184 results on '"Brown adipocytes"'
Search Results
2. Transplantation of fat tissues and iPSC-derived energy expenditure adipocytes to counteract obesity-driven metabolic disorders: Current strategies and future perspectives
- Author
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Christian Dani, Vincent Dani, and Xi Yao
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Brown Adipocytes ,Endocrinology, Diabetes and Metabolism ,Induced Pluripotent Stem Cells ,Metabolic disorders ,Adipose tissue ,030209 endocrinology & metabolism ,Bioinformatics ,Article ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Adipose Tissue, Brown ,Metabolic Diseases ,iPSC-derived adipocytes ,Diabetes mellitus ,medicine ,Humans ,Obesity ,Beneficial effects ,Transplantation ,business.industry ,Thermogenesis ,Adipose tissues ,Surgical procedures ,medicine.disease ,Adipocytes, Brown ,Energy expenditure ,Energy Metabolism ,business - Abstract
Several therapeutic options have been developed to address the obesity epidemic and treat associated metabolic diseases. Despite the beneficial effects of surgery and drugs, effective therapeutic solutions have been held back by the poor long-term efficiency and detrimental side effects. The development of alternative approaches is thus urgently required. Fat transplantation is common practice in many surgical procedures, including aesthetic and reconstructive surgery, and is a budding future direction for treating obesity-related metabolic defects. This review focuses on adipose tissue transplantation and the recent development of cell-based therapies to boost the mass of energy-expenditure cells. Brown adipocyte transplantation is a promising novel therapy to manage obesity and associated metabolic disorders, but the need to have an abundant and relevant source of brown fat tissue or brown adipocytes for transplantation is a major hurdle to overcome. Current studies have focused on the rodent model to obtain a proof of concept of a tissue-transplantation strategy able to achieve effective long-term effects to reverse metabolic defects in obese patients. Future perspectives and opportunities to develop innovative human fat tissue models and 3D engineered hiPSC-adipocytes are discussed.
- Published
- 2021
3. Local acetate inhibits brown adipose tissue function
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Wenfei Sun, Christian Wolfrum, and Hua Dong
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Male ,medicine.medical_specialty ,obesity ,Medical Sciences ,Brown Adipocytes ,Adipose Tissue, White ,Citric Acid Cycle ,Gene Expression ,Acetates ,Diet, High-Fat ,Transcriptome ,Paracrine signalling ,Eating ,Mice ,Adipose Tissue, Brown ,Internal medicine ,Brown adipose tissue ,medicine ,Animals ,Multidisciplinary ,Chemistry ,Gene Expression Profiling ,Thermogenesis ,brown adipose tissue ,Biological Sciences ,acetate ,RNA-seq ,Citric acid cycle ,Mice, Inbred C57BL ,Endocrinology ,medicine.anatomical_structure ,Adipocytes, Brown ,Energy expenditure ,Gene Expression Regulation ,Energy Metabolism ,Function (biology) - Abstract
Brown adipose tissue has been extensively studied in the last decade for its potential to counteract the obesity pandemic. However, the paracrine regulation within brown tissue is largely unknown. Here, we show that local acetate directly inhibits brown fat thermogenesis, without changing acetate levels in the circulation. We demonstrate that modulating acetate within brown tissue at physiological levels blunts its function and systemically decreases energy expenditure. Using a series of transcriptomic analyses, we identified genes related to the tricarboxylic acid cycle and brown adipocyte formation, which are down-regulated upon local acetate administration. Overall, these findings demonstrate that local acetate inhibits brown fat function., Proceedings of the National Academy of Sciences of the United States of America, 118 (49), ISSN:0027-8424, ISSN:1091-6490
- Published
- 2021
4. Asparagine reinforces mTORC1 signaling to boost thermogenesis and glycolysis in adipose tissues
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Dongning Pan, Huiru Tang, Qingwen Zhao, Xuan Cui, Qi Wang, Yingjiang Xu, Xiaoyan Xu, Qi-Qun Tang, Ting Shi, Linyu Yan, and Xiaoxuan Xu
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Male ,brown adipocytes ,medicine.medical_specialty ,Adipose tissue ,Mechanistic Target of Rapamycin Complex 1 ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,Energy homeostasis ,Mice ,chemistry.chemical_compound ,Internal medicine ,medicine ,Animals ,Metabolomics ,Glycolysis ,Asparagine ,mTORC1 ,Molecular Biology ,Beta oxidation ,Cells, Cultured ,General Immunology and Microbiology ,Fatty acid metabolism ,General Neuroscience ,Thermogenesis ,asparagine ,Articles ,glycolysis ,Cold Temperature ,Metabolism ,Endocrinology ,Gene Expression Regulation ,chemistry ,Lipogenesis ,Signal Transduction - Abstract
Brown and beige fat are specialized for energy expenditure by dissipating energy from glucose and fatty acid oxidation as heat. While glucose and fatty acid metabolism have been extensively studied in thermogenic adipose tissues, the involvement of amino acids in regulating adaptive thermogenesis remains little studied. Here, we report that asparagine supplementation in brown and beige adipocytes drastically upregulated the thermogenic transcriptional program and lipogenic gene expression, so that asparagine‐fed mice showed better cold tolerance. In mice with diet‐induced obesity, the asparagine‐fed group was more responsive to β3‐adrenergic receptor agonists, manifesting in blunted body weight gain and improved glucose tolerance. Metabolomics and 13C‐glucose flux analysis revealed that asparagine supplement spurred glycolysis to fuel thermogenesis and lipogenesis in adipocytes. Mechanistically, asparagine stimulated the mTORC1 pathway, which promoted expression of thermogenic genes and key enzymes in glycolysis. These findings show that asparagine bioavailability affects glycolytic and thermogenic activities in adipose tissues, providing a possible nutritional strategy for improving systemic energy homeostasis., Adipocyte energy dissipation is fueled by the non‐essential amino acid asparagine via an mTORC1‐4E‐BP1‐glycolysis axis.
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- 2021
5. PD21-11 BROWN ADIPOCYTES COULD PREVENT URINARY STONES IN THE HUMAN BODY
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Atsushi Okada, Kazumi Taguchi, Shuzo Hamamoto, Takahiro Yasui, Ryosuke Ando, Teruaki Sugino, and Rei Unno
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medicine.medical_specialty ,Endocrinology ,Brown Adipocytes ,business.industry ,Urology ,Urinary system ,Internal medicine ,medicine ,Metabolic syndrome ,medicine.disease ,business - Abstract
INTRODUCTION AND OBJECTIVE:Brown adipocytes consume energy and are known to improve metabolic syndrome. In previous studies using mice that brown adipocytes could prevent the formation of urinary s...
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- 2021
6. Brown Fat Dnmt3b Deficiency Ameliorates Obesity in Female Mice
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Shirong Wang, Xin Cui, Huidong Shi, Bingzhong Xue, Fenfen Li, Hang Shi, and Jia Jing
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brown adipocytes ,medicine.medical_specialty ,obesity ,Science ,DNMT3B ,Biology ,Dnmt3b ,General Biochemistry, Genetics and Molecular Biology ,Article ,Insulin resistance ,Downregulation and upregulation ,Internal medicine ,medicine ,Epigenetics ,thermogenesis ,Ecology, Evolution, Behavior and Systematics ,Paleontology ,medicine.disease ,Obesity ,Endocrinology ,Space and Planetary Science ,DNA methylation ,Knockout mouse ,embryonic structures ,Thermogenesis - Abstract
Obesity results from a chronic energy imbalance due to energy intake exceeding energy expenditure. Activation of brown fat thermogenesis has been shown to combat obesity. Epigenetic regulation, including DNA methylation, has emerged as a key regulator of brown fat thermogenic function. Here we aimed to study the role of Dnmt3b, a DNA methyltransferase involved in de novo DNA methylation, in the regulation of brown fat thermogenesis and obesity. We found that the specific deletion of Dnmt3b in brown fat promotes the thermogenic and mitochondrial program in brown fat, enhances energy expenditure, and decreases adiposity in female mice fed a regular chow diet. With a lean phenotype, the female knockout mice also exhibit increased insulin sensitivity. In addition, Dnmt3b deficiency in brown fat also prevents diet-induced obesity and insulin resistance in female mice. Interestingly, our RNA-seq analysis revealed an upregulation of the PI3K-Akt pathway in the brown fat of female Dnmt3b knockout mice. However, male Dnmt3b knockout mice have no change in their body weight, suggesting the existence of sexual dimorphism in the brown fat Dnmt3b knockout model. Our data demonstrate that Dnmt3b plays an important role in the regulation of brown fat function, energy metabolism and obesity in female mice.
- Published
- 2021
7. Dnmt3b Deficiency in Myf5+-Brown Fat Precursor Cells Promotes Obesity in Female Mice
- Author
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Qiang Cao, Fenfen Li, Xin Cui, Hang Shi, Huidong Shi, Bingzhong Xue, Shirong Wang, and Jia Jing
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0301 basic medicine ,brown adipocytes ,medicine.medical_specialty ,obesity ,Methyltransferase ,DNMT3B ,Biology ,Dnmt3b ,Biochemistry ,Microbiology ,Energy homeostasis ,Article ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Genetic model ,medicine ,MEF2C ,Epigenetics ,Molecular Biology ,epigenetics ,thermogenesis ,QR1-502 ,030104 developmental biology ,Endocrinology ,embryonic structures ,MYF5 ,Thermogenesis ,030217 neurology & neurosurgery - Abstract
Increasing energy expenditure through activation of brown fat thermogenesis is a promising therapeutic strategy for the treatment of obesity. Epigenetic regulation has emerged as a key player in regulating brown fat development and thermogenic program. Here, we aimed to study the role of DNA methyltransferase 3b (Dnmt3b), a DNA methyltransferase involved in de novo DNA methylation, in the regulation of brown fat function and energy homeostasis. We generated a genetic model with Dnmt3b deletion in brown fat-skeletal lineage precursor cells (3bKO mice) by crossing Dnmt3b-floxed (fl/fl) mice with Myf5-Cre mice. Female 3bKO mice are prone to diet-induced obesity, which is associated with decreased energy expenditure. Dnmt3b deficiency also impairs cold-induced thermogenic program in brown fat. Surprisingly, further RNA-seq analysis reveals a profound up-regulation of myogenic markers in brown fat of 3bKO mice, suggesting a myocyte-like remodeling in brown fat. Further motif enrichment and pyrosequencing analysis suggests myocyte enhancer factor 2C (Mef2c) as a mediator for the myogenic alteration in Dnmt3b-deficient brown fat, as indicated by decreased methylation at its promoter. Our data demonstrate that brown fat Dnmt3b is a key regulator of brown fat development, energy metabolism and obesity in female mice.
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- 2021
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8. Involvement of TRP Channels in Adipocyte Thermogenesis: An Update
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Yixuan Luo, Fei Zhang, Wuping Sun, Tao Zhu, and Shuo Tang
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0301 basic medicine ,brown adipocytes ,medicine.medical_specialty ,obesity ,QH301-705.5 ,Energy metabolism ,Adipose tissue ,Review ,Biology ,Body weight ,03 medical and health sciences ,Transient receptor potential channel ,chemistry.chemical_compound ,Cell and Developmental Biology ,0302 clinical medicine ,Internal medicine ,Adipocyte ,Brown adipose tissue ,energy metabolism ,medicine ,Biology (General) ,Human obesity ,calcium ,TRP channels ,Cell Biology ,thermogenesis ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,chemistry ,030220 oncology & carcinogenesis ,beige adipocytes ,Thermogenesis ,Developmental Biology - Abstract
Obesity prevalence became a severe global health problem and it is caused by an imbalance between energy intake and expenditure. Brown adipose tissue (BAT) is a major site of mammalian non-shivering thermogenesis or energy dissipation. Thus, modulation of BAT thermogenesis might be a promising application for body weight control and obesity prevention. TRP channels are non-selective calcium-permeable cation channels mainly located on the plasma membrane. As a research focus, TRP channels have been reported to be involved in the thermogenesis of adipose tissue, energy metabolism and body weight regulation. In this review, we will summarize and update the recent progress of the pathological/physiological involvement of TRP channels in adipocyte thermogenesis. Moreover, we will discuss the potential of TRP channels as future therapeutic targets for preventing and combating human obesity and related-metabolic disorders.
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- 2021
9. Sex Differences in Brown Adipose Tissue Function: Sex Hormones, Glucocorticoids, and Their Crosstalk
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Jenny A. Visser, Aldo Grefhorst, and Kasiphak Kaikaew
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Male ,0301 basic medicine ,brown adipocytes ,Endocrinology, Diabetes and Metabolism ,steroid receptors ,Physiology ,Adipose tissue ,White adipose tissue ,Review ,Overweight ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,Energy homeostasis ,Mice ,0302 clinical medicine ,Endocrinology ,Adipose Tissue, Brown ,Brown adipose tissue ,Homeostasis ,Gonadal Steroid Hormones ,glucocorticoids ,Thermogenesis ,Lipids ,Adipocytes, Brown ,medicine.anatomical_structure ,Female ,medicine.symptom ,sex characteristics ,Sex characteristics ,estrogens ,Hypothalamo-Hypophyseal System ,030209 endocrinology & metabolism ,Biology ,progesterone ,03 medical and health sciences ,Sex Factors ,SDG 3 - Good Health and Well-being ,medicine ,Animals ,Humans ,Obesity ,lcsh:RC648-665 ,sex chromosomes ,androgens ,Lipid Metabolism ,medicine.disease ,Rats ,030104 developmental biology ,Diabetes Mellitus, Type 2 ,Hormone - Abstract
Excessive fat accumulation in the body causes overweight and obesity. To date, research has confirmed that there are two types of adipose tissue with opposing functions: lipid-storing white adipose tissue (WAT) and lipid-burning brown adipose tissue (BAT). After the rediscovery of the presence of metabolically active BAT in adults, BAT has received increasing attention especially since activation of BAT is considered a promising way to combat obesity and associated comorbidities. It has become clear that energy homeostasis differs between the sexes, which has a significant impact on the development of pathological conditions such as type 2 diabetes. Sex differences in BAT activity may contribute to this and, therefore, it is important to address the underlying mechanisms that contribute to sex differences in BAT activity. In this review, we discuss the role of sex hormones in the regulation of BAT activity under physiological and some pathological conditions. Given the increasing number of studies suggesting a crosstalk between sex hormones and the hypothalamic-pituitary-adrenal axis in metabolism, we also discuss this crosstalk in relation to sex differences in BAT activity.
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- 2021
10. Brown Adipose Tissue Heterogeneity, Energy Metabolism, and Beyond
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Abhijit Babaji Shinde, Anying Song, and Qiong A. Wang
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0301 basic medicine ,medicine.medical_specialty ,obesity ,Brown Adipocytes ,Endocrinology, Diabetes and Metabolism ,Energy metabolism ,Endocrine System ,Mice, Transgenic ,Type 2 diabetes ,Review ,Biology ,Diseases of the endocrine glands. Clinical endocrinology ,Mitochondrial Proteins ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Endocrinology ,Adipose Tissue, Brown ,Metabolic Diseases ,Internal medicine ,Brown adipose tissue ,medicine ,Adipocytes ,Animals ,Homeostasis ,Humans ,brown adipocyte development ,Cholesterol homeostasis ,Uncoupling Protein 1 ,Independent research ,Fatty Acids ,Thermogenesis ,medicine.disease ,RC648-665 ,Thermogenin ,Mitochondria ,030104 developmental biology ,medicine.anatomical_structure ,Adipocytes, Brown ,brown adipocyte energy metabolism ,Energy Metabolism ,030217 neurology & neurosurgery ,brown adipocyte heterogeneity - Abstract
Brown adipocyte in brown adipose tissue (BAT) specializes in expending energy through non-shivering thermogenesis, a process that produces heat either by uncoupling protein 1 (UCP1) dependent uncoupling of mitochondrial respiration or by UCP1 independent mechanisms. Apart from this, there is ample evidence suggesting that BAT has an endocrine function. Studies in rodents point toward its vital roles in glucose and lipid homeostasis, making it an important therapeutic target for treating metabolic disorders related to morbidities such as obesity and type 2 diabetes. The rediscovery of thermogenically active BAT depots in humans by several independent research groups in the last decade has revitalized interest in BAT as an even more promising therapeutic intervention. Over the last few years, there has been overwhelming interest in understanding brown adipocyte’s developmental lineages and how brown adipocyte uniquely utilizes energy beyond UCP1 mediated uncoupling respiration. These new discoveries would be leveraged for designing novel therapeutic interventions for metabolic disorders.
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- 2021
11. Brown adipocytes and β3-stimulant-induced brown-like adipocytes contribute to the prevention of renal crystal formation
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Hitoshi Yamashita, Tohru Mogami, Atsushi Okada, Kazumi Taguchi, Takahiro Yasui, Shuzo Hamamoto, Kenjiro Kohri, Rei Unno, Ryosuke Ando, and Teruaki Sugino
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0301 basic medicine ,medicine.medical_specialty ,Physiology ,Brown Adipocytes ,Chemistry ,medicine.medical_treatment ,030232 urology & nephrology ,medicine.disease ,Stimulant ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Endocrinology ,Internal medicine ,medicine ,Kidney stones ,Metabolic syndrome - Abstract
According to recent studies, kidney stones are associated with metabolic syndrome. We focused on brown adipocytes and β3-stimulant-induced brown-like adipocytes to investigate how these adipocytes influence kidney stone disease. For the interscapular brown adipose tissue (iBAT) removal experiment, mice were subjected to either iBAT removal or sham operation (X-BAT group or sham group), and, after 3 wk, renal crystal deposition was induced by intra-abdominal injection of glyoxylate (GOX) for 6 days. For the β3-stimulant experiment, mice were administered intra-abdominal injections of the β3-stimulant (β3-group) or saline (control group) for 6 days. Thereafter, renal crystal deposition was induced by intra-abdominal injection of GOX for 6 days. iBAT removal decreased the expression of Sod1 and increased that of chemokine (C-C motif) ligand 2 ( Ccl2), EGF module-containing mucin-like receptor 1 ( Emr1), and tumor necrosis factor ( Tnf) in the kidneys. Renal crystal deposition was 2.06-fold higher in the X-BAT group than in the sham group. The β3-stimulant caused differentiation of white adipocytes into brown-like adipocytes. In the kidneys of the β3-group, the expression of Ccl2 and Emr1 decreased and that of Sod1 increased. Renal crystal deposition was 0.17-fold lower in the β3-group than in the control group. In summary, iBAT removal promoted kidney inflammation and renal crystal formation. β3-Stimulant-induced brown-like adipocytes reduced inflammation and improved antioxidant action in the kidneys, which suppressed renal crystal formation. This is the first report on the therapeutic role of brown and brown-like adipocytes for kidney stone formation.
- Published
- 2019
12. Role of estradiol and testosterone in Ucp1 expression in brown/beige adipocytes
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Mitsuyuki Shirai, Osamu Hashimoto, Masayuki Funaba, Tohru Matsui, Masaru Murakami, Teruo Kawada, and Mika Suzuki
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0301 basic medicine ,Agonist ,medicine.medical_specialty ,medicine.drug_class ,Brown Adipocytes ,Clinical Biochemistry ,Cell Biology ,General Medicine ,Biology ,Beige Adipocytes ,Biochemistry ,Thermogenin ,03 medical and health sciences ,030104 developmental biology ,Endocrinology ,Adipogenesis ,Internal medicine ,medicine ,Receptor ,Testosterone ,Hormone - Abstract
Activity of brown/beige adipocytes is higher in women than in men. The expression level of uncoupling protein 1 (UCP1) is largely consistent with the thermogenic activity in brown/beige adipocytes. The present study examined the direct effects of sex hormones on Ucp1 expression in brown adipocytes and beige adipocytes, which were differentiated from HB2 brown preadipocytes and 3T3-L1 white preadipocytes, respectively; treatment with estradiol or testosterone was used during the early (days 0-8) or late stage (days 8-12) of brown adipogenesis and beige adipogenesis. On day 8 or day 12, cells were treated with or without isoproterenol (Iso), an agonist for the β-adrenergic receptor, for 4 hours. Furthermore, the sex of cells was examined; the sex-determining region y gene, which is located on the y chromosome, was present in HB2 cells, but not in 3T3-L1 cells, suggesting that HB2 cells and 3T3-L1 cells are male and female cells, respectively. Treatment with 17β-estradiol during the early stage of brown adipogenesis enhanced the responsiveness to Iso on Ucp1 induction, whereas treatment during the late stage of brown adipogenesis decreased Ucp1 expression in unstimulated brown adipocytes. Estradiol decreased Iso-induced Ucp1 expression during the early stage of beige adipogenesis. Treatment with testosterone during the early stage of brown adipogenesis did not affect Ucp1 expression but increased the responsiveness to Iso on Ucp1 induction by the treatment during the late stage of brown adipogenesis. The present results suggest that sex hormones modulate the expression level of Ucp1 in brown/beige adipocytes in a stage-dependent manner. Direct effects of sex hormones in brown/beige adipogenesis were evaluated. Treatment with 17β-estradiol during the early stage of brown adipogenesis enhanced the responsiveness to isoproterenol (Iso), an agonist for the β-adrenergic receptor, on Ucp1 induction, whereas treatment during the late stage of brown adipogenesis decreased Ucp1 expression in unstimulated brown adipocytes. Estradiol decreased Iso-induced Ucp1 expression during the early stage of beige adipogenesis. Testosterone during the late stage of brown adipogenesis increased the responsiveness to Iso on Ucp1 induction. Sex hormones modulate the expression level of Ucp1 in brown/beige adipocytes in a stage-dependent manner.
- Published
- 2018
13. Deficiency in interleukin-18 promotes differentiation of brown adipose tissue resulting in fat accumulation despite dyslipidemia
- Author
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Hisato Matsunaga, Haruki Okamura, Yuko Watanabe, Hiromichi Yamanishi, Kaoru Ikubo, Wen Li, Seishi Maeda, Sachi Kuwahara-Otani, Kyosuke Yamanishi, Naomi Gamachi, Keiji Nakasho, Takuya Hashimoto, Keiichiro Mukai, Daisuke Okuzaki, and Yosif El-Darawish
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,FGF21 ,Adipose tissue ,lcsh:Medicine ,Brown adipose tissue ,General Biochemistry, Genetics and Molecular Biology ,Proinflammatory cytokine ,03 medical and health sciences ,Adipose Tissue, Brown ,Internal medicine ,medicine ,Animals ,Adiposity ,Dyslipidemias ,PRDM16 ,Adipogenesis ,Chemistry ,Brown adipocytes ,Research ,Stem Cells ,lcsh:R ,Interleukin-18 ,Cell Differentiation ,Thermogenesis ,General Medicine ,Thermogenin ,Recombinant Proteins ,Fatty Liver ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Lipid metabolism ,Interleukin-18 knockout ,Differentiation Inducer - Abstract
Background The cytokine, interleukin-18 (IL-18), was originally identified as an interferon-γ-inducing proinflammatory factor; however, there is increasing evidence suggesting that it has non-immunological effects on physiological functions. We have previously investigated the potential pathophysiological relationship between IL-18 and dyslipidemia, non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, which were mediated by lipid energy imbalance. Therefore, herein we focused on brown adipocytes (BAs) and brown adipose tissue (BAT) related to energy consumption as non-shivering thermogenesis. Methods Il18−/− male mice were generated on the C57Bl/6 background, and littermate C57Bl/6 Il18+/+ male mice were used as controls. To reveal the direct effect of IL-18, primary cell cultures derived from both mice were established. Moreover, for molecular analysis, microarray, quantitative reverse transcription PCR and western blotting were performed using 6 and 12 weeks old mice. To evaluate the short- and long-term effects of IL-18 on BAT, recombinant IL-18 was administered for 2 and 12 weeks, respectively. Results Compared with Il18+/+ mice, BAT of Il18−/− mice showed earlier differentiation and lipid accumulation. To examine the direct effect of IL-18 on BAT, BA cell cultures were established. Myogenic factor 5-expressing adipose precursor cells were extracted from Il18+/+ and Il18−/− mice. PR domain containing 16 (PRDM16), a differentiation inducer, was strongly expressed in Il18−/− BAs, and uncoupling protein 1, a thermogenic and differentiation marker, was upregulated, resulting in the promotion of BA differentiation. Moreover, PRDM16-dependent and independent molecules related to BAT function, such as fibroblast growth factor 21, were activated. These findings were confirmed by comparing Il18+/+ and Il18−/− mice at 6 and 12 weeks of age. Additional analyses of the molecular mechanisms influencing the ‘Quantity of adipocytes’ identified three associated genes, apolipoprotein C3 (Apoc3), insulin-induced gene 1 (Insig1) and vitamin D (1,25-dihydroxyvitamin D3) receptor (Vdr). Intravenous administration of IL-18 not only significantly improved the expression of some of these genes, but it also significantly decreased the adipocytes’ size. Conclusions This study demonstrated the critical function of IL-18 in differentiation and lipid metabolism in BAs. Furthermore, IL-18 may contribute to novel treatments by improving the energy imbalance. Electronic supplementary material The online version of this article (10.1186/s12967-018-1684-3) contains supplementary material, which is available to authorized users.
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- 2018
14. NanoSIMS imaging reveals unexpected heterogeneity in nutrient uptake by brown adipocytes
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Yiping Tu, Ken Matsumoto, Patrick J. Heizer, Haibo Jiang, Holger Gerhardt, Peter Tontonoz, Xuchen Hu, Rachel S. Jung, Rochelle M Ellison, Thomas A. Weston, Loren G. Fong, Cuiwen He, and Stephen G. Young
- Subjects
0301 basic medicine ,Gastric gavage ,medicine.medical_specialty ,Brown Adipocytes ,Lipoproteins ,Biophysics ,Spectrometry, Mass, Secondary Ion ,Adipose tissue ,White adipose tissue ,Biochemistry ,Article ,03 medical and health sciences ,13c enrichment ,Nutrient ,Internal medicine ,Brown adipose tissue ,medicine ,Animals ,Molecular Biology ,Receptors, Lipoprotein ,Carbon Isotopes ,Chemistry ,Metabolic heterogeneity ,Fatty Acids ,Nutrients ,Cell Biology ,Lipids ,Mice, Mutant Strains ,Mice, Inbred C57BL ,Adipocytes, Brown ,Glucose ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure - Abstract
Heterogeneity in the metabolic properties of adipocytes in white adipose tissue has been well documented. We sought to investigate metabolic heterogeneity in adipocytes of brown adipose tissue (BAT), focusing on heterogeneity in nutrient uptake. To explore the possibility of metabolic heterogeneity in brown adipocytes, we used nanoscale secondary ion mass spectrometry (NanoSIMS) to quantify uptake of lipids in adipocytes interscapular BAT and perivascular adipose tissue (PVAT) after an intravenous injection of triglyceride-rich lipoproteins (TRLs) containing [(2)H]triglycerides ((2)H-TRLs). The uptake of deuterated lipids into brown adipocytes was quantified by NanoSIMS. We also examined (13)C enrichment in brown adipocytes after administering [(13)C]glucose or (13)C-labeled mixed fatty acids by gastric gavage. The uptake of (2)H-TRLs-derived lipids into brown adipocytes was heterogeneous, with (2)H enrichment in adjacent adipocytes varying by more than fourfold. We also observed substantial heterogeneity in (13)C enrichment in adjacent brown adipocytes after administering [(13)C]glucose or [(13)C]fatty acids by gastric gavage. The uptake of nutrients by adjacent brown adipocytes within a single depot is variable, suggesting that there is heterogeneity in the metabolic properties of brown adipocytes.
- Published
- 2018
15. AKAP1 Deficiency Attenuates Diet‐Induced Obesity and Insulin Resistance by Promoting Fatty Acid Oxidation and Thermogenesis in Brown Adipocytes
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Jing Zhao, Linjie He, Bingchao Qi, Fengzhou Liu, Yilin Zhao, Fei Kang, Tian Gao, Gang Wang, Haitao Guo, Yuanfang He, Fei Li, Ya Zhao, Jinliang Xing, Qichao Huang, and Lele Ji
- Subjects
medicine.medical_specialty ,Brown Adipocytes ,General Chemical Engineering ,diet‐induced obesity ,General Physics and Astronomy ,Medicine (miscellaneous) ,Adipose tissue ,02 engineering and technology ,010402 general chemistry ,fatty acid β‐oxidation ,01 natural sciences ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,Insulin resistance ,Internal medicine ,insulin resistance ,medicine ,General Materials Science ,lcsh:Science ,Beta oxidation ,chemistry.chemical_classification ,Full Paper ,General Engineering ,Fatty acid ,mitochondrial thermogenesis ,AKAP1 ,Full Papers ,021001 nanoscience & nanotechnology ,medicine.disease ,Obesity ,0104 chemical sciences ,Endocrinology ,chemistry ,Phosphorylation ,lcsh:Q ,0210 nano-technology ,Thermogenesis - Abstract
Altering the balance between energy intake and expenditure is a major strategy for treating obesity. Nonetheless, despite the progression in antiobesity drugs on appetite suppression, therapies aimed at increasing energy expenditure are limited. Here, knockout ofAKAP1, a signaling hub on outer mitochondrial membrane, renders mice resistant to diet‐induced obesity.AKAP1 knockout significantly enhances energy expenditure and thermogenesis in brown adipose tissues (BATs) of obese mice. Restoring AKAP1 expression in BAT clearly reverses the beneficial antiobesity effect in AKAP1−/− mice. Mechanistically, AKAP1 remarkably decreases fatty acid β‐oxidation (FAO) by phosphorylating ACSL1 to inhibit its activity in a protein‐kinase‐A‐dependent manner and thus inhibits thermogenesis in brown adipocytes. Importantly, AKAP1 peptide inhibitor effectively alleviates diet‐induced obesity and insulin resistance. Altogether, the findings demonstrate that AKAP1 functions as a brake of FAO to promote diet‐induced obesity, which may be used as a potential therapeutic target for obesity., In high‐fat‐diet‐treated mice, A kinase anchoring protein 1 (AKAP1) functions as a brake molecule of fatty acid β‐oxidation by recruiting protein kinase A (PKA) and acyl‐CoA synthetase long chain family member 1 (ACSL1) to the outer mitochondrial membrane and inhibiting mitochondrial ACSL1 activity through PKA. AKAP1 elimination enhances mitochondrial ACSL1 activity and increases brown adipose thermogenesis, preventing mice from obesity.
- Published
- 2021
16. Androgen Receptors in Multiple Organ Systems Provide Molecular Gateways to Polycystic Ovary Syndrome
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Jon E. Levine, Daniel A. Dumesic, and David H. Abbott
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Male ,medicine.medical_specialty ,Brown Adipocytes ,Mice ,Endocrinology ,Internal medicine ,Commentaries ,medicine ,Humans ,Macrophage ,Animals ,White Adipocytes ,Organ system ,Mice, Knockout ,business.industry ,Hyperandrogenism ,Brain ,Dihydrotestosterone ,medicine.disease ,Polycystic ovary ,Androgen receptor ,Disease Models, Animal ,medicine.anatomical_structure ,Adipose Tissue ,Receptors, Androgen ,Androgens ,Female ,Neuron ,business ,Polycystic Ovary Syndrome - Abstract
Polycystic ovary syndrome (PCOS) is a complex disorder characterized by endocrine, reproductive, and metabolic abnormalities. Despite PCOS being the most common endocrinopathy affecting women of reproductive age, the etiology of PCOS is poorly understood, so there is no cure and symptomatic treatment is suboptimal. Hyperandrogenism is the most consistent feature observed in PCOS patients, and recently aberrant neuroendocrine signaling and adipose tissue function have been proposed as playing a role in the development of PCOS. To investigate the role of adipose tissue and the brain as key sites for androgen receptor (AR)-mediated development of PCOS, we combined a white and brown adipose and brain-specific AR knockout (AdBARKO) mouse model with a dihydrotestosterone (DHT)-induced mouse model of PCOS. As expected, in wildtype (WT) control females, DHT exposure induced the reproductive PCOS traits of cycle irregularity, ovulatory dysfunction, and reduced follicle health, whereas in AdBARKO females, DHT did not produce the reproductive features of PCOS. The metabolic PCOS characteristics of increased adiposity, adipocyte hypertrophy, and hepatic steatosis induced by DHT in WT females were not evident in DHT-treated AdBARKO females, which displayed normal white adipose tissue weight and no adipocyte hypertrophy or liver steatosis. Dihydrotestosterone treatment induced increased fasting glucose levels in both WT and AdBARKO females. These findings demonstrate that adipose tissue and the brain are key loci of androgen-mediated actions involved in the developmental origins of PCOS. These data support targeting adipocyte and neuroendocrine AR-driven pathways in the future development of novel therapeutic strategies for PCOS.
- Published
- 2020
17. UCP1 Dependent and Independent Thermogenesis in Brown and Beige Adipocytes
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Tetsuya Yamada and Kenji Ikeda
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0301 basic medicine ,Brown Adipocytes ,Mini Review ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,Energy homeostasis ,adipogenesis ,03 medical and health sciences ,Endocrinology ,0302 clinical medicine ,Animals ,Humans ,Adipocytes, Beige ,Uncoupling Protein 1 ,lcsh:RC648-665 ,Chemistry ,Thermogenesis ,Calcium cycling ,Beige Adipocytes ,Mitochondrial respiration ,beige adipocyte ,Thermogenin ,Cell biology ,thermogenic fat ,030104 developmental biology ,Adipocytes, Brown ,Adipogenesis ,brown adipocyte - Abstract
Mammals have two types of thermogenic adipocytes: brown adipocytes and beige adipocytes. Thermogenic adipocytes express high levels of uncoupling protein 1 (UCP1) to dissipates energy in the form of heat by uncoupling the mitochondrial proton gradient from mitochondrial respiration. There is much evidence that UCP1 is the center of BAT thermogenesis and systemic energy homeostasis. Recently, UCP1 independent thermogenic pathway identified in thermogenic adipocytes. Importantly, the thermogenic pathways are different in brown and beige adipocytes. Ca2+-ATPase 2b calcium cycling mechanism is selective to beige adipocytes. It remains unknown how the multiple thermogenic mechanisms are coordinately regulated. The discovery of UCP1-independent thermogenic mechanisms potential offer new opportunities for improving obesity and type 2 diabetes particularly in groups such as elderly and obese populations who do not possess UCP1 positive adipocytes.
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- 2020
18. PPARγ and PPARα synergize to induce robust browning of white fat in vivo
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Anna Lindblom, Andrea Ahnmark, Matthew J. Harms, Stefanie Maurer, Tobias Kroon, Laurianne Bonnet, Daniel Nilsson, Victoria Osinski, Jeremie Boucher, Ida Alexandersson, Peter Gennemark, Gavin O'Mahony, and Coleen A. McNamara
- Subjects
0301 basic medicine ,Male ,FGF21 ,Adipocytes, White ,Peroxisome proliferator-activated receptor ,Adipose tissue ,FGF21, fibroblast growth factor 21 ,White adipose tissue ,PPAR ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,iWAT, inguinal WAT ,Adipose Tissue, Brown ,iBAT, interscapular BAT ,Uncoupling Protein 1 ,chemistry.chemical_classification ,Brown adipocytes ,Thermogenesis ,WAT, white adipose tissue ,TG, triglycerides ,TN, thermoneutrality ,Thermogenin ,DIO, diet-induced obese ,Adipocytes, Brown ,RT, room temperature ,Original Article ,TZD, thiazolidinedione ,Rosiglitazone ,medicine.drug ,medicine.medical_specialty ,lcsh:Internal medicine ,UCP1 ,Tesaglitazar ,Adipose Tissue, White ,030209 endocrinology & metabolism ,QUICKI, quantitative insulin-sensitivity check index ,eWAT, epididymal WAT ,PPAR, peroxisome proliferator-activated receptors ,03 medical and health sciences ,Beige adipocytes ,Internal medicine ,UCP1, uncoupling protein 1 ,medicine ,Animals ,PPAR alpha ,lcsh:RC31-1245 ,Molecular Biology ,Activator (genetics) ,EE, energy expenditure ,Cell Biology ,BAT, brown adipose tissue ,Mice, Inbred C57BL ,PPAR gamma ,030104 developmental biology ,Endocrinology ,chemistry ,Energy Metabolism ,Transcription Factors - Abstract
Objective Peroxisome proliferator-activated receptors (PPARs) are key transcription factors that regulate adipose development and function, and the conversion of white into brown-like adipocytes. Here we investigated whether PPARα and PPARγ activation synergize to induce the browning of white fat. Methods A selection of PPAR activators was tested for their ability to induce the browning of both mouse and human white adipocytes in vitro, and in vivo in lean and obese mice. Results All dual PPARα/γ activators tested robustly increased uncoupling protein 1 (Ucp1) expression in both mouse and human adipocytes in vitro, with tesaglitazar leading to the largest Ucp1 induction. Importantly, dual PPARα/γ activator tesaglitazar strongly induced browning of white fat in vivo in both lean and obese male mice at thermoneutrality, greatly exceeding the increase in Ucp1 observed with the selective PPARγ activator rosiglitazone. While selective PPARγ activation was sufficient for the conversion of white into brown-like adipocytes in vitro, dual PPARα/γ activation was superior to selective PPARγ activation at inducing white fat browning in vivo. Mechanistically, the superiority of dual PPARα/γ activators is mediated at least in part via a PPARα-driven increase in fibroblast growth factor 21 (FGF21). Combined treatment with rosiglitazone and FGF21 resulted in a synergistic increase in Ucp1 mRNA levels both in vitro and in vivo. Tesaglitazar-induced browning was associated with increased energy expenditure, enhanced insulin sensitivity, reduced liver steatosis, and an overall improved metabolic profile compared to rosiglitazone and vehicle control groups. Conclusions PPARγ and PPARα synergize to induce robust browning of white fat in vivo, via PPARγ activation in adipose, and PPARα-mediated increase in FGF21., Graphical abstract Dual PPARα/γ activation is superior to selective PPARγ activation at inducing browning of white fat in vivo: via PPARγ action in the adipose and a PPARα-mediated action in the liver resulting in increased circulating fibroblast growth factor 21 (FGF21).Image 1, Highlights • Dual PPARα/γ activators robustly induce browning of white fat in vitro and in vivo. • PPARγ action alone is sufficient to convert white into brown-like adipocytes in vitro. • Dual PPARα/γ activators are superior to PPARγ activators for browning of white fat in vivo. • PPARγ action in adipose and PPARα-mediated increase in FGF21 synergize to induce browning of white fat in vivo.
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- 2020
19. Human Pluripotent Stem Cells: A Relevant Model to Identify Pathways Governing Thermogenic Adipocyte Generation
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Xi Yao, Christian Dani, Vincent Dani, Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), RUIZ, Caroline, Université Nice Sophia Antipolis (1965 - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
- Subjects
0301 basic medicine ,brown adipocytes ,Cell type ,obesity ,[SDV]Life Sciences [q-bio] ,cell-based therapy ,Endocrinology, Diabetes and Metabolism ,Cell ,adipocyte progenitors ,Adipose tissue ,030209 endocrinology & metabolism ,Review ,Biology ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,drug discovery ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Adipocyte ,medicine ,Progenitor cell ,Induced pluripotent stem cell ,lcsh:RC648-665 ,Embryonic stem cell ,Cell biology ,[SDV] Life Sciences [q-bio] ,human induced pluripotent stem cells ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Signal transduction - Abstract
International audience; Brown and brown-like adipocytes (BAs) are promising cell targets to counteract obesity thanks to their potential to drain and oxidize circulating glucose and triglycerides. However, the scarcity of BAs in human adults is a major limitation for energy expenditure based therapies. Enhanced characterization of BA progenitor cells (BAPs) and identification of critical pathways regulating their generation and differentiation into mature BAs would be an effective way to increase the BA mass. The identification of molecular mechanisms involved in the generation of thermogenic adipocytes is progressing substantially in mice. Much less is known in humans, thus highlighting the need for an in vitro model of human adipocyte development. Pluripotent stem cells (PSCs), i.e., embryonic stem cells and induced pluripotent stem cells, help gain insight into the different phases in the development of multiple cell types. We will discuss the capacity of human PSCs to differentiate into BAs in this review. Several groups, including ours, have reported low spontaneous adipocyte generation from PSCs. However, factors governing the differentiation of induced pluripotent stem cell-derived BA progenitors cells were recently identified, and the TGFβ signaling pathway has a pivotal role. The development of new relevant methods, such as the differentiation of hPSC-BAPs into 3D adipospheres to better mimick the lobular structure of human adipose tissue, will also be discussed. Differentiation of human PSCs into thermogenic adipocytes at high frequency provides an opportunity to characterize new targets for anti-obesity therapy.
- Published
- 2020
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20. 3-Iodothyronamine Affects Thermogenic Substrates' Mobilization in Brown Adipocytes
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Annunziatina Laurino, Grazia Chiellini, Elisa Landucci, Laura Raimondi, Daniela Buonvicino, Manuela Gencarelli, and Costanza Mazzantini
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0301 basic medicine ,brown adipocytes ,medicine.medical_specialty ,Glucose uptake ,3-iodothyronamine ,030209 endocrinology & metabolism ,CREB ,Article ,General Biochemistry, Genetics and Molecular Biology ,BAs ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,Downregulation and upregulation ,Internal medicine ,Brown adipose tissue ,medicine ,insulin-stimulated glucose uptake ,lcsh:QH301-705.5 ,Protein kinase B ,General Immunology and Microbiology ,biology ,Adrenergic receptors ,Brown adipocytes ,Insulin-stimulated glucose uptake ,Lipolysis ,T1AM ,T3 ,Thyroid hormone ,Thyroid hormone metabolites ,thyroid hormone metabolites ,adrenergic receptors ,lipolysis ,thyroid hormone ,AMPK ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,lcsh:Biology (General) ,biology.protein ,General Agricultural and Biological Sciences ,GLUT4 - Abstract
We investigated the effect of 3-iodothyronamine (T1AM) on thermogenic substrates in brown adipocytes (BAs). BAs isolated from the stromal fraction of rat brown adipose tissue were exposed to an adipogenic medium containing insulin in the absence (M) or in the presence of 20 nM T1AM (M+T1AM) for 6 days. At the end of the treatment, the expression of p-PKA/PKA, p-AKT/AKT, p-AMPK/AMPK, p-CREB/CREB, p-P38/P38, type 1 and 3 beta adrenergic receptors (β1–β3AR), GLUT4, type 2 deiodinase (DIO2), and uncoupling protein 1 (UCP-1) were evaluated. The effects of cell conditioning with T1AM on fatty acid mobilization (basal and adrenergic-mediated), glucose uptake (basal and insulin-mediated), and ATP cell content were also analyzed in both cell populations. When compared to cells not exposed, M+T1AM cells showed increased p-PKA/PKA, p-AKT/AKT, p-CREB/CREB, p-P38/P38, and p-AMPK/AMPK, downregulation of DIO2 and β1AR, and upregulation of glycosylated β3AR, GLUT4, and adiponectin. At basal conditions, glycerol release was higher for M+T1AM cells than M cells, without any significant differences in basal glucose uptake. Notably, in M+T1AM cells, adrenergic agonists failed to activate PKA and lipolysis and to increase ATP level, but the glucose uptake in response to insulin exposure was more pronounced than in M cells. In conclusion, our results suggest that BAs conditioning with T1AM promote a catabolic condition promising to fight obesity and insulin resistance.
- Published
- 2020
21. Adipose tissue dysfunction in cancer cachexia
- Author
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Gheyath K. Nasrallah, Sahar I. Da'as, and Balsam Rizeq
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brown adipocytes ,0301 basic medicine ,medicine.medical_specialty ,white adipocytes ,Cachexia ,Physiology ,WAT browning ,Adipose Tissue, White ,Clinical Biochemistry ,Adipokine ,Adipose tissue ,White adipose tissue ,Proinflammatory cytokine ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Adipokines ,Adipose Tissue, Brown ,Weight loss ,Neoplasms ,Adipocyte ,Internal medicine ,Brown adipose tissue ,medicine ,Humans ,Muscle, Skeletal ,Pancreas ,Inflammation ,business.industry ,Brain ,Cancer ,Cell Biology ,Lipid Metabolism ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Liver ,chemistry ,inflammation ,030220 oncology & carcinogenesis ,Cytokines ,medicine.symptom ,business ,hormones, hormone substitutes, and hormone antagonists ,cancer cachexia - Abstract
Cancer cachexia is a complex disorder that is driven by inflammation and metabolic imbalances, resulting in extreme weight loss. Adipose tissue, a main player in cancer cachexia, is an essential metabolic and secretory organ consisting of both white adipose tissue (WAT) and brown adipose tissue. Its secretory products, including adipokines and cytokines, affect a wide variety of central and peripheral organs, such as the skeletal muscle, brain, pancreas, and liver. Therefore, a combination of metabolic alterations, and systemic inflammation dysregulation of both anti-inflammatory and proinflammatory modulators contribute toward adipose tissue wasting in cancer cachexia. Growing evidence suggests that, during cancer cachexia, WAT undergoes a browning process, resulting in increased lipid mobilization and energy expenditure. In this review, we have summarized the characteristics of cancer cachexia and WAT browning. Furthermore, this review describes how adipose tissue becomes inflamed in cancer, shedding light on the combinatorial action of multiple secreted macromolecules, cytokines, hormones, and tumor mediators on adipose tissue dysfunction. We also highlight the inflammatory responses, energy utilization defects, and molecular mechanisms underlying the WAT dysfunction and browning in cancer cachexia. Further, the actual mechanisms behind the loss of adipose tissue are unknown, but have been attributed to increased adipocyte lipolysis, systemic inflammation, and apoptosis or reduced lipogenesis. The understanding of adipose tissue dysfunction in cancer cachexia will hopefully promote the development of new therapeutic approaches to prevent or treat this wasting syndrome. Qatar University funding the project: GCC Co-Fund Program Grant: GCC-2017-001.
- Published
- 2018
22. Novel Aspects of White Adipose Tissue Browning by Thyroid Hormones
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Kerstin Krause
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0301 basic medicine ,endocrine system ,medicine.medical_specialty ,Sympathetic nervous system ,Thyroid Hormones ,Sympathetic Nervous System ,endocrine system diseases ,Brown Adipocytes ,Endocrinology, Diabetes and Metabolism ,Adipose Tissue, White ,Adipose tissue ,030209 endocrinology & metabolism ,White adipose tissue ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Adipose Tissue, Brown ,Internal medicine ,Brown adipose tissue ,Internal Medicine ,medicine ,Browning ,Adipocytes ,Animals ,Humans ,business.industry ,Thermogenesis ,General Medicine ,030104 developmental biology ,medicine.anatomical_structure ,Thyroid hormones ,business - Abstract
Thyroid hormones are essential for the full thermogenic capacity of brown adipose tissue. The thermogenic response of brown adipocytes to thyroid hormones is resulting from the synergistic interaction of thyroid hormones with the sympathetic nervous system. In recent years, evidence has been provided that thyroid hormones also induce the browning of white adipose tissues. This review will provide a brief overview about the recent findings regarding the effects of thyroid hormones on adipose tissue thermogenesis including central and peripheral regulation of white adipose tissue browning.
- Published
- 2019
23. Promotion of lipid storage rather than of thermogenic competence by fetal versus newborn calf serum in primary cultures of brown adipocytes
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Barbara Cannon, Jasper M. A. de Jong, and Jan Nedergaard
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brown adipocytes ,Male ,Serum ,medicine.medical_specialty ,UCP1 ,Histology ,adipose conversion ,Cell ,Cell Culture Techniques ,Adipose tissue ,DIO2 ,newborn calf serum ,Biology ,norepinephrine ,Mice ,Fetus ,Internal medicine ,Gene expression ,medicine ,Animals ,Cells, Cultured ,fetal bovine serum ,Thermogenesis ,Cell Biology ,differentiation ,Lipid Metabolism ,Lipids ,Culture Media ,Endocrinology ,medicine.anatomical_structure ,Adipocytes, Brown ,Animals, Newborn ,Cattle ,Rosiglitazone ,Fetal bovine serum ,medicine.drug ,Research Paper - Abstract
Much current understanding of brown adipocyte development comes from in-vitro cell models. Serum type may affect the behavior of cultured cells and thus conclusions drawn. Here, we investigate effects of serum type (“fetal bovine” versus “newborn calf”) on responses to differentiation inducers (the PPARγ agonist rosiglitazone or the neurotransmitter norepinephrine) in cultured primary brown adipocytes. Lipid storage was enhanced by fetal versus newborn serum. However, molecular adipose conversion (Pparg2 and Fabp4 expression) was not affected by serum type. Rosiglitazone-induced (7-days) expression of thermogenic genes (i.e. Ucp1, Pgc1a, Dio2 and Elovl3) was not systematically affected by serum type. However, importantly, acute (2 h) norepinephrine-induced thermogenic gene expression was overall markedly higher (and adipose genes somewhat lower) in cells cultured in newborn serum. Thus, newborn serum promotes thermogenic competence, and the use of fetal serum in brown adipocyte cultures (as is often routine) counteracts adequate differentiation. Agents that counteract this inhibition may therefore confoundingly be ascribed genuine thermogenic competence-inducing properties.
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- 2018
24. The effects of different time of melatonin administration on differentiation and functional status of the brown adipocytes in vivo
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M. Dzerzhinsky and O. Kalmukova
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Transplantation ,medicine.medical_specialty ,business.industry ,Brown Adipocytes ,Biomedical Engineering ,Melatonin ,Endocrinology ,In vivo ,Internal medicine ,Immunology and Allergy ,Medicine ,Functional status ,business ,Biotechnology ,medicine.drug - Published
- 2018
25. Effects of α-(prazosin and yohimbine) and β-receptors activity on cAMP generation and UCP1 gene expression in brown adipocytes
- Author
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Hirendra M Biswas
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Physiology ,Brown Adipocytes ,Mice ,Norepinephrine ,03 medical and health sciences ,0302 clinical medicine ,Adipose Tissue, Brown ,Internal medicine ,Receptors, Adrenergic, beta ,Drug Discovery ,Cyclic AMP ,medicine ,Prazosin ,Animals ,RNA, Messenger ,Uncoupling Protein 1 ,Pharmacology ,Chemistry ,Ucp1 gene ,Yohimbine ,General Medicine ,Receptors, Adrenergic, alpha ,β receptor ,030104 developmental biology ,Endocrinology ,Thermogenesis ,030217 neurology & neurosurgery ,medicine.drug - Abstract
Background Brown adipose tissue (BAT) contains both α- and β-adrenergic receptors. In the literature, the activity of α-adrenoreceptors is less documented, and their functions still remain puzzling. The present investigation has been undertaken to understand α-adrenoreceptors’ activity and their relation between uncoupling protein 1 (UCP1) mRNA expression and cyclic AMP (cAMP) generation in BAT. Methods BAT precursor cells from young mice were grown in culture. Cells were exposed to norepinephrine (NE) and other agents. RNA was isolated after harvesting the cells, and northern blot was performed. Filters were exposed to film after hybridization with nick-translated complementary DNA probes, and results were evaluated by scanning. Amersham assay kit was used for cAMP measurement. Results Treatment of prazosin and yohimbine separately with 1 μM of NE shows stimulation of UCP1 mRNA expression 106% and 154%, respectively, whereas with that of both drugs shows only 76%. cAMP generation occurs 282% with prazosin, 100% with yohimbine, and 382% with both drugs with 1 μM of NE, whereas it is 310%, 40%, and 358%, respectively, with 10 μM of NE. Conclusions Stimulation of thermogenesis after treatment of prazosin and NE may be due to the inhibition of phosphodiesterase enzyme and with yohimbine and NE indicates the possibility of inhibition of the inhibitory effect of α2- and stimulation of α1-receptors. Increase of cAMP concentration with yohimbine and both drugs with NE are not correlated to UCP1 mRNA expression. This indicates that the relationship between cAMP elevation and stimulation of thermogenesis is not simple. This study clearly shows the interaction between β- and α-adrenoreceptor activities.
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- 2018
26. Food-derived regulatory factors against obesity and metabolic syndrome
- Author
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Teruo Kawada
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Brown Adipocytes ,Adipose Tissue, White ,Adipose tissue ,Inflammation ,Applied Microbiology and Biotechnology ,Biochemistry ,Analytical Chemistry ,03 medical and health sciences ,Insulin resistance ,Adipose Tissue, Brown ,Functional Food ,Internal medicine ,Adipocytes ,medicine ,Humans ,Nutritional Physiological Phenomena ,Obesity ,Molecular Biology ,Metabolic Syndrome ,business.industry ,Organic Chemistry ,Thermogenesis ,General Medicine ,Lipid Metabolism ,medicine.disease ,030104 developmental biology ,Endocrinology ,Chronic Disease ,Tumor necrosis factor alpha ,Metabolic syndrome ,medicine.symptom ,Energy Metabolism ,business ,Biotechnology - Abstract
Obesity is a key factor in metabolic syndrome. The study of metabolic syndrome focuses on the anti-weight gain properties of physiological mechanisms and food components. Abnormal energy metabolism is a major risk factor of metabolic syndrome. Chronic inflammation is a feature of obesity; cytokines from hypertrophied adipocytes cause inflammation in both adipose tissue and blood vessels, resulting in symptoms of metabolic syndrome. Tumor necrosis factor-α causes insulin resistance in adipocytes and regression of brown adipocytes, resulting in abnormal energy metabolism. Functional foods can serve as a strategy for prevention and treatment of obesity linked with metabolic processes in white and brown adipose tissues. Diet-induced thermogenesis caused by certain food components stimulates burning of stored fat within adipose tissues. A mechanistic understanding of dietary thermogenesis via the sympathetic nerve system will prove valuable for the development of precise strategies for the practical prevention of metabolic syndrome.
- Published
- 2018
27. Effect of ambient temperature on the proliferation of brown adipocyte progenitors and endothelial cells during postnatal BAT development in Syrian hamsters
- Author
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Kazuki Nagaya, Ayumi Tsubota, Kazuhiro Kimura, Yuko Okamatsu-Ogura, Junko Nio-Kobayashi, and Shohei Nakagiri
- Subjects
Male ,Vascular Endothelial Growth Factor A ,0301 basic medicine ,Cell physiology ,medicine.medical_specialty ,Physiology ,Brown Adipocytes ,Biology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Adipose Tissue, Brown ,Adipocyte ,Internal medicine ,Brown adipose tissue ,Adipocytes ,medicine ,Animals ,Progenitor cell ,Uncoupling Protein 1 ,Cell Proliferation ,Mesocricetus ,Temperature ,Endothelial Cells ,Thermogenin ,Staining ,Vascular endothelial growth factor ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Female ,030217 neurology & neurosurgery - Abstract
In Syrian hamsters, brown adipose tissue (BAT) develops postnatally through the proliferation and differentiation of brown adipocyte progenitors. In the study reported here, we investigated how ambient temperature influenced BAT formation in neonatal hamsters. In both hamsters raised at 23 or 30 °C, the interscapular fat changed from white to brown coloration in an age-dependent manner and acquired the typical morphological features of BAT by day 16. However, the expression of uncoupling protein 1, a brown adipocyte marker, and of vascular endothelial growth factor α were lower in the group raised at 30 °C than in that raised at 23 °C. Immunofluorescent staining revealed that the proportion of Ki67-expressing progenitors and endothelial cells was lower in the 30 °C group than in the 23 °C group. These results indicate that warm ambient temperature suppresses the proliferation of brown adipocyte progenitors and endothelial cells and negatively affects the postnatal development of BAT in Syrian hamsters.
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- 2018
28. Restricting glycolysis impairs brown adipocyte glucose and oxygen consumption
- Author
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Marie S. Isidor, Amanda Cheung, Bjørn Quistorff, Astrid L. Basse, Jacob B. Hansen, Sally Winther, and Nina B Skjoldborg
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Cold stimulation ,Physiology ,Brown Adipocytes ,Endocrinology, Diabetes and Metabolism ,Down-Regulation ,chemistry.chemical_element ,Biology ,Oxygen ,Mice ,03 medical and health sciences ,Oxygen Consumption ,Adipose Tissue, Brown ,Downregulation and upregulation ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,Glycolysis ,Cells, Cultured ,Glycolytic enzymes ,Fatty Acids ,Isoproterenol ,Thermogenesis ,Adrenergic beta-Agonists ,Lipid Metabolism ,Adipocytes, Brown ,Glucose ,030104 developmental biology ,Endocrinology ,chemistry ,Oxidation-Reduction - Abstract
During thermogenic activation, brown adipocytes take up large amounts of glucose. In addition, cold stimulation leads to an upregulation of glycolytic enzymes. Here we have investigated the importance of glycolysis for brown adipocyte glucose consumption and thermogenesis. Using siRNA-mediated knockdown in mature adipocytes, we explored the effect of glucose transporters and glycolytic enzymes on brown adipocyte functions such as consumption of glucose and oxygen. Basal oxygen consumption in brown adipocytes was equally dependent on glucose and fatty acid oxidation, whereas isoproterenol (ISO)-stimulated respiration was fueled mainly by fatty acids, with a significant contribution from glucose oxidation. Knockdown of glucose transporters in brown adipocytes not only impaired ISO-stimulated glycolytic flux but also oxygen consumption. Diminishing glycolytic flux by knockdown of the first and final enzyme of glycolysis, i.e., hexokinase 2 (HK2) and pyruvate kinase M (PKM), respectively, decreased glucose uptake and ISO-stimulated oxygen consumption. HK2 knockdown had a more severe effect, which, in contrast to PKM knockdown, could not be rescued by supplementation with pyruvate. Hence, brown adipocytes rely on glucose consumption and glycolytic flux to achieve maximum thermogenic output, with glycolysis likely supporting thermogenesis not only by pyruvate formation but also by supplying intermediates for efferent metabolic pathways.
- Published
- 2018
29. Brown adipocytes can display a mammary basal myoepithelial cell phenotype in vivo
- Author
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Elżbieta Król, Min Li, Chaoqun Niu, Guanlin Wang, Ting Li, Wanzhu Jin, Li Li, John R. Speakman, and Baoguo Li
- Subjects
0301 basic medicine ,medicine.medical_specialty ,lcsh:Internal medicine ,Adipocytes, White ,Population ,Mammary gland ,Adipose tissue ,Mice, Transgenic ,Biology ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Mammary Glands, Animal ,Adipocyte ,Lactation ,Internal medicine ,medicine ,Animals ,Adipocytes, Beige ,Obesity ,education ,lcsh:RC31-1245 ,Molecular Biology ,Uncoupling Protein 1 ,education.field_of_study ,Adipogenesis ,Brown adipocytes ,Myoepithelial cell ,Epithelial Cells ,Thermogenesis ,Cell Biology ,Basal myoepithelial cells ,Gene signature ,Phenotype ,Beige/brite adipocytes ,Adipocytes, Brown ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Female ,Original Article - Abstract
Objective Previous work has suggested that white adipocytes may also show a mammary luminal secretory cell phenotype during lactation. The capacity of brown and beige/brite adipocytes to display a mammary cell phenotype and the levels at which they demonstrate such phenotypes in vivo is currently unknown. Methods To investigate the putative adipocyte origin of mammary gland cells, we performed genetic lineage-labeling experiments in BAT and the mammary glands. Results These studies indicated that the classic brown adipocytes (Ucp1+) and subcutaneous beige/brite adipocytes (Ucp1−/+) were found in the mammary gland during lactation, when they exhibited a mammary myoepithelial phenotype. Up to 2.5% of the anterior dorsal interscapular mammary myoepithelial cell population had a brown adipocyte origin with an adipose and myoepithelial gene signature during lactation. Eliminating these cells, along with all the brown adipocytes, significantly slowed offspring growth, potentially demonstrating their functional importance. Additionally, we showed mammary epithelial lineage Mmtv+ and Krt14+ cells expressed brown adipocyte markers after weaning, demonstrating that mammary gland cells can display an adipose phenotype. Conclusions The identification of a brown adipocyte origin of mammary myoepithelial cells provides a novel perspective on the interrelationships between adipocytes and mammary cells with implications for our understanding of obesity and breast cancer., Highlights • Brown adipocytes can show a mammary myoepithelial cell phenotype in vivo. • Myf5+/Ucp1+ myoepithelial cells express an adipose and myoepithelial signature. • Mammary-derived epithelial cells can display adipose features after weaning.
- Published
- 2017
30. Difference in intracellular temperature rise between matured and precursor brown adipocytes in response to uncoupler and β-adrenergic agonist stimuli
- Author
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Kumiko Ikado, Hideki Koizumi, Toshikazu Tsuji, Kazuaki Kajimoto, and Seiichi Uchiyama
- Subjects
0301 basic medicine ,Agonist ,Male ,medicine.medical_specialty ,Brown Adipocytes ,medicine.drug_class ,Polymers ,Science ,Intracellular Space ,Stimulation ,Thermometry ,Biology ,Article ,Fluorescence ,Norepinephrine (medication) ,03 medical and health sciences ,Precursor cell ,Internal medicine ,medicine ,Animals ,Rats, Wistar ,Receptor ,Cells, Cultured ,Multidisciplinary ,Cell Death ,Uncoupling Agents ,Antagonist ,Temperature ,Adrenergic beta-Agonists ,Cell biology ,030104 developmental biology ,Endocrinology ,Adipocytes, Brown ,Medicine ,Intracellular ,medicine.drug - Abstract
Brown adipocytes function to maintain body temperature by heat production. However, direct measurement of heat production at a single cell level remains difficult. Here we developed a method to measure the temperature within primary cultured brown adipocytes using a cationic fluorescent polymeric thermometer. Placement of the thermometer within a matured brown adipocyte and a precursor cell enabled the detection of heat production following uncoupler treatment. The increase in the intracellular temperature due to stimulation with a mitochondrial uncoupler was higher in matured brown adipocytes than in precursor cells. Stimulation with a β-adrenergic receptor (β-AR) agonist, norepinephrine, raised the intracellular temperature of matured brown adipocytes to a level comparable to that observed after stimulation with a β3-AR-specific agonist, CL316.243. In contrast, neither β-AR agonist induced an intracellular temperature increase in precursor cells. Further, pretreatment of brown adipocytes with a β3-AR antagonist inhibited the norepinephrine-stimulated elevation of temperature. These results demonstrate that our novel method successfully determined the difference in intracellular temperature increase between matured brown adipocytes and precursor cells in response to stimulation by an uncoupler and β-AR agonists.
- Published
- 2017
31. Creatine supplementation and thermogenesis in humans—a futile exercise?
- Author
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Christian Wolfrum and Salvatore Modica
- Subjects
medicine.medical_specialty ,business.industry ,Brown Adipocytes ,Futile cycle ,Endocrinology, Diabetes and Metabolism ,Lipid metabolism ,Cell Biology ,Metabolism ,Creatine ,medicine.disease ,Obesity ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Physiology (medical) ,Internal medicine ,Internal Medicine ,Medicine ,business ,Young female ,Thermogenesis - Abstract
A creatine futile cycle has been shown to contribute to energy expenditure in beige adipocytes in preclinical mouse models of obesity. In this issue of Nature Metabolism, Connell and colleagues show that creatine supplementation in healthy young female vegetarians unfortunately affects neither human brown adipocyte activity nor cold-induced energy expenditure.
- Published
- 2021
32. Circadian control of brown adipose tissue
- Author
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Maaike E. Straat, Sander Kooijman, Mariëtte R. Boon, Rick Hogenboom, and Patrick C.N. Rensen
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Shift work ,Brown Adipocytes ,030209 endocrinology & metabolism ,Biology ,03 medical and health sciences ,0302 clinical medicine ,Rhythm ,Adipose Tissue, Brown ,Internal medicine ,Brown adipose tissue ,medicine ,Animals ,Humans ,Endocrine system ,Circadian rhythm ,Molecular Biology ,Brown adipocytes ,Cardiometabolic health ,Cell Biology ,Lipids ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Increased risk - Abstract
Disruption of circadian (similar to 24 h) rhythms is associated with an increased risk of cardiometabolic diseases. Therefore, unravelling how circadian rhythms are regulated in different metabolic tissues has become a prominent research focus. Of particular interest is brown adipose tissue (BAT), which combusts triglyceride-derived fatty acids and glucose into heat and displays a circannual and diurnal rhythm in its thermogenic activity. In this review, the genetic, neuronal and endocrine generation of these rhythms in BAT is discussed. In addition, the potential risks of disruption or attenuation of these rhythms in BAT, and possible factors influencing these rhythms, are addressed.
- Published
- 2021
33. Brown and brite adipocytes: Same function, but different origin and response
- Author
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Dinh-Toi Chu and Barbara Gawronska-Kozak
- Subjects
Adult ,0301 basic medicine ,medicine.medical_specialty ,Brown Adipocytes ,Adipose tissue ,Biology ,Biochemistry ,03 medical and health sciences ,Internal medicine ,medicine ,Animals ,Humans ,Adipocytes, Beige ,Obesity ,Uncoupling Protein 1 ,Adipogenesis ,Infant, Newborn ,Thermogenesis ,General Medicine ,Beige Adipocytes ,Human being ,Gene expression profiling ,Adipocytes, Brown ,030104 developmental biology ,Endocrinology ,Brite Adipocytes ,Function (biology) - Abstract
Inducing brown adipocytes in white adipose tissues is a promising target to combat obesity and its related disorders in human beings. This goal has been especially encouraged by new important discoveries of human brown adipose tissues. The accumulating evidence confirms the presence of active brown adipocytes, not only in newborns, but also in adult humans. In rodents, there are two populations of the Ucp1-expressing adipocytes with well characterized-thermogenic functions, classical interscapular brown adipocytes and brite/beige adipocytes (brown adipocytes that are induced in white adipose tissues). Importantly, the anatomical localization, gene expression profiling and functional characterization of Ucp1-expressing fat cells indicates brite and brown adipocytes coexist in human beings. Therefore, the research directions of brown and brite adipogenesis provide lead to potential new therapies to fight obesity and its related metabolic diseases in human being. The objectives of this review are (1) to discuss the fate of primary adipocytes based on tissue origins, and (2) to discuss mechanisms of brown and brite adipogenesis which could lead to their different responses to browning reagents.
- Published
- 2017
34. The β3-adrenergic receptor is dispensable for browning of adipose tissues
- Author
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Barbara Cannon, René T. F. Wouters, Jan Nedergaard, Jasper M. A. de Jong, Nathalie Boulet, and Natasa Petrovic
- Subjects
0301 basic medicine ,medicine.medical_specialty ,β3 adrenergic receptor ,Physiology ,Brown Adipocytes ,Endocrinology, Diabetes and Metabolism ,Adipose tissue ,Biology ,Beige Adipocytes ,Cell biology ,03 medical and health sciences ,030104 developmental biology ,Endocrinology ,Physiology (medical) ,Internal medicine ,medicine ,Browning - Abstract
Brown and brite/beige adipocytes are attractive therapeutic targets to treat metabolic diseases. To maximally utilize their functional potential, further understanding is required about their identities and their functional differences. Recent studies with β3-adrenergic receptor knockout mice reported that brite/beige adipocytes, but not classical brown adipocytes, require the β3-adrenergic receptor for cold-induced transcriptional activation of thermogenic genes. We aimed to further characterize this requirement of the β3-adrenergic receptor as a functional distinction between classical brown and brite/beige adipocytes. However, when comparing wild-type and β3-adrenergic receptor knockout mice, we observed no differences in cold-induced thermogenic gene expression ( Ucp1, Pgc1a, Dio2, and Cidea) in brown or white (brite/beige) adipose tissues. Irrespective of the duration of the cold exposure or the sex of the mice, we observed no effect of the absence of the β3-adrenergic receptor. Experiments with the β3-adrenergic receptor agonist CL-316,243 verified the functional absence of β3-adrenergic signaling in these knockout mice. The β3-adrenergic receptor knockout model in the present study was maintained on a FVB/N background, whereas earlier reports used C57BL/6 and 129Sv mice. Thus our data imply background-dependent differences in adrenergic signaling mechanisms in response to cold exposure. Nonetheless, the present data indicate that the β3-adrenergic receptor is dispensable for cold-induced transcriptional activation in both classical brown and, as opposed to earlier studies, brite/beige cells.
- Published
- 2017
35. Loss of MyoD Promotes Fate Transdifferentiation of Myoblasts Into Brown Adipocytes
- Author
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Feng Yue, Yaohui Nie, Chao Wang, Mulan Qaher, Weiyi Liu, Shihuan Kuang, Hannah Elizabeth Horton, and Atsushi Asakura
- Subjects
0301 basic medicine ,Male ,lcsh:Medicine ,MyoD ,Receptor, IGF Type 1 ,Myoblasts ,Brown adipose tissue ,Cells, Cultured ,PRDM16 ,Mice, Knockout ,lcsh:R5-920 ,Adipogenesis ,Myogenesis ,Reverse Transcriptase Polymerase Chain Reaction ,Brown adipocytes ,General Medicine ,musculoskeletal system ,Cell biology ,DNA-Binding Proteins ,medicine.anatomical_structure ,Adipocytes, Brown ,MYF5 ,CRISPR-Cas9 ,lcsh:Medicine (General) ,C2C12 ,tissues ,Research Paper ,Signal Transduction ,medicine.medical_specialty ,animal structures ,Satellite Cells, Skeletal Muscle ,Blotting, Western ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,03 medical and health sciences ,MyoD Protein ,Internal medicine ,medicine ,Animals ,Base Sequence ,lcsh:R ,MicroRNAs ,030104 developmental biology ,Endocrinology ,Gene Expression Regulation ,Microscopy, Fluorescence ,Animal Sciences ,Cell Transdifferentiation ,Repressor ,CRISPR-Cas Systems ,Proto-Oncogene Proteins c-akt ,Transcription Factors - Abstract
Brown adipose tissue (BAT) represents a promising agent to ameliorate obesity and other metabolic disorders. However, the abundance of BAT decreases with age and BAT paucity is a common feature of obese subjects. As brown adipocytes and myoblasts share a common Myf5 lineage origin, elucidating the molecular mechanisms underlying the fate choices of brown adipocytes versus myoblasts may lead to novel approaches to expand BAT mass. Here we identify MyoD as a key negative regulator of brown adipocyte development. CRISPR/CAS9-mediated deletion of MyoD in C2C12 myoblasts facilitates their adipogenic transdifferentiation. MyoD knockout downregulates miR-133 and upregulates the miR-133 target Igf1r, leading to amplification of PI3K–Akt signaling. Accordingly, inhibition of PI3K or Akt abolishes the adipogenic gene expression of MyoD null myoblasts. Strikingly, loss of MyoD converts satellite cell-derived primary myoblasts to brown adipocytes through upregulation of Prdm16, a target of miR-133 and key determinant of brown adipocyte fate. Conversely, forced expression of MyoD in brown preadipocytes blocks brown adipogenesis and upregulates the expression of myogenic genes. Importantly, miR-133a knockout significantly blunts the inhibitory effect of MyoD on brown adipogenesis. Our results establish MyoD as a negative regulator of brown adipocyte development by upregulating miR-133 to suppress Akt signaling and Prdm16., Highlights • Loss of MyoD facilitates adipogenic transdifferentiation of myoblasts. • Overexpression of MyoD transdifferentiate brown preadipocytes to myoblasts. • MyoD acts partially through miR-133 to suppress brown adipocyte cell fate. Brown fat burns fat to produce heat, and represents a promising agent to treat obesity and its related disorders. Brown fat cells and muscle cells share a common origin, but what controls the developmental separation of the two cell types is not well understood. This study reports that inhibition of “MyoD” gene in muscle progenitors promotes their differentiation into brown fat cells in mice. Conversely, forced expression of MyoD in brown fat progenitors converts them into muscle cells. This work suggests that inhibition of MyoD may represent a future direction to expand brown fat and alleviate obesity in humans.
- Published
- 2017
36. Modulation of brown adipocyte activity by milk by-products: Stimulation of brown adipogenesis by buttermilk
- Author
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Ryosuke Kida, Masayuki Funaba, Kengo Muto, Ken Kato, Teruo Kawada, Takayuki Y. Nara, Tohru Matsui, Hiroki Asano, and Osamu Hashimoto
- Subjects
0301 basic medicine ,Agonist ,medicine.medical_specialty ,medicine.drug_class ,Brown Adipocytes ,Chemistry ,Clinical Biochemistry ,Stimulation ,Cell Biology ,General Medicine ,Biochemistry ,Thermogenin ,03 medical and health sciences ,030104 developmental biology ,Endocrinology ,Energy expenditure ,Downregulation and upregulation ,Adipogenesis ,Internal medicine ,medicine ,Receptor - Abstract
Brown adipocytes dissipate chemical energy in the form of heat through the expression of mitochondrial uncoupling protein 1 (Ucp1); Ucp1 expression is further upregulated by the stimulation of β-adrenergic receptors in brown adipocytes. An increase in energy expenditure by activated brown adipocytes potentially contributes to the prevention of or therapeutics for obesity. The present study examined the effects of milk by-products, buttermilk and butter oil, on brown adipogenesis and the function of brown adipocytes. The treatment with buttermilk modulated brown adipogenesis, depending on the product tested; during brown adipogenesis, buttermilk 1 inhibited the differentiation of HB2 brown preadipocytes. In contrast, buttermilk 3 and 5 increased the expression of Ucp1 in the absence of isoproterenol (Iso), a β-adrenergic receptor agonist, suggesting the stimulation of brown adipogenesis. In addition, the Iso-induced expression of Ucp1 was enhanced by buttermilk 2 and 3. The treatment with buttermilk did not affect the basal or induced expression of Ucp1 by Iso in HB2 brown adipocytes, except for buttermilk 5, which increased the basal expression of Ucp1. Conversely, butter oil did not significantly affect the expression of Ucp1, irrespective of the cell phase of HB2 cells, ie, treatment during brown adipogenesis or of brown adipocytes. The results of the present study indicate that buttermilk is a regulator of brown adipogenesis and suggest its usefulness as a potential food material for antiobesity.
- Published
- 2016
37. Human thermogenic adipocytes: a reflection on types of adipocyte, developmental origin, and potential application
- Author
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Yang Tao and Dinh-Toi Chu
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Physiology ,Fat content ,Brown Adipocytes ,Adipocytes, White ,Biology ,Models, Biological ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Adipocyte ,Internal medicine ,medicine ,Animals ,Humans ,Glucose homeostasis ,Adipocytes, Beige ,Obesity ,Adiposity ,Adipogenesis ,Insulin sensitivity ,Thermogenesis ,General Medicine ,medicine.disease ,Capillaries ,3. Good health ,Adipocytes, Brown ,030104 developmental biology ,Endocrinology ,chemistry ,Brite Adipocytes ,Insulin Resistance ,Stromal Cells - Abstract
Obesity is a leading health problem facing the modern world; however, no effective therapy for this health issue has yet been developed. A promising research direction to identify novel therapies to prevent obesity has emerged from discoveries on development and function of brown/brite adipocytes in mammals. Importantly, there is evidence for the presence and function of active thermogenic brown adipocytes in both infants and adult humans. Several new investigations have shown that thermogenic adipocytes are beneficial to maintain glucose homeostasis, insulin sensitivity, and a healthy body fat content. Such thermogenic adipocytes have been considered as targets to develop a therapy for preventing obesity. This short review seeks to highlight recent findings on the development and function of brown/brite adipocytes in humans and to discuss potential treatments based on these adipocytes to reduce obesity and its related disorders.
- Published
- 2016
38. Fat tissues, the brite and the dark sides
- Author
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Alexander Pfeifer, Ruping Pan, and Yong Chen
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Physiology ,Brown Adipocytes ,Clinical Biochemistry ,Adipose tissue ,White adipose tissue ,Biology ,Brown adipose tissue ,Brite/beige adipocytes ,03 medical and health sciences ,Broad spectrum ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,Humans ,Adipocytes, Beige ,Obesity ,Invited Review ,medicine.disease ,Adipocytes, Brown ,Metabolism ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Brite Adipocytes ,Energy expenditure ,Energy Metabolism ,Whole body - Abstract
Fat tissue is well known for its capacity to store energy and its detrimental role in obesity and metaflammation. However, humans possess different types of fat that have different functions in physiology and metabolic diseases. Apart from white adipose tissue (WAT), the body’s main energy storage, there is also brown adipose tissue (BAT) that dissipates energy as a defense against cold and maintains energy balance for the whole body. BAT is present not only in newborns but also in adult humans and its mass correlates with leanness. Moreover, “brown-like” adipocytes have been detected in human WAT. These “brown-in-white” (brite) or beige cells can be induced by cold and a broad spectrum of pharmacological substances and, therefore, they are also known as “inducible brown adipocytes.” Activation of brown and/or brite adipocytes reduces metabolic diseases, at least in murine models of obesity. Thus, brown/brite adipocytes represent the “brite” side of fat and are potential targets for novel therapeutic approaches for treatment of obesity and obesity-associated diseases.
- Published
- 2016
39. Analysis of the effects of age-related changes in the microenvironment on brown adipocyte formation and function
- Author
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S Gohlke, TJ Schulz, and C Mancini
- Subjects
medicine.medical_specialty ,Endocrinology ,Brown Adipocytes ,Internal medicine ,Age related ,medicine ,Biology ,Function (biology) - Published
- 2019
40. In vitro Radiopharmaceutical Evidence for MCHR1 Binding Sites in Murine Brown Adipocytes
- Author
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Theresa Balber, Katarína Benčurová, Florian Wolfgang Kiefer, Oana Cristina Kulterer, Eva-Maria Klebermass, Gerda Egger, Loan Tran, Karl-Heinz Wagner, Helmut Viernstein, Katharina Pallitsch, Helmut Spreitzer, Marcus Hacker, Wolfgang Wadsak, Markus Mitterhauser, and Cécile Philippe
- Subjects
brown adipocytes ,0301 basic medicine ,Beta-3 adrenergic receptor ,Endocrinology, Diabetes and Metabolism ,adrenergic beta-3 receptor ,[18F]FE@SNAP ,030209 endocrinology & metabolism ,Adrenergic beta-3 Receptor Agonists ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,03 medical and health sciences ,Endocrinology ,0302 clinical medicine ,In vivo ,Brown adipose tissue ,medicine ,Binding site ,Receptor ,Original Research ,Messenger RNA ,lcsh:RC648-665 ,MCHR1 ,Chemistry ,BAT ,[11C]SNAP-7941 ,melanin-concentrating hormone receptor 1 ,Cell biology ,PET ,030104 developmental biology ,medicine.anatomical_structure ,Hormone receptor - Abstract
[11C]SNAP-7941 and its radiofluorinated, fluoro-ethyl derivative [18F]FE@SNAP have been developed as the first positron emission tomography tracers for melanin-concentrating hormone receptor 1 (MCHR1) imaging. Accumulation of these MCHR1 PET-tracers in rat brown adipose tissue (BAT) in vivo provided first indication of MCHR1 expression in rodent BAT. To rule out off-target binding, affinity of both MCHR1 ligands towards adrenergic beta-3 receptors (ADRB3) was examined. Further, specific binding of [11C]SNAP-7941 to brown adipocytes and effects of MCHR1 ligands on brown adipocyte activation were investigated. SNAP-7941 and FE@SNAP evinced to be highly selective towards MCHR1. [11C]SNAP-7941 binding to brown adipocytes was shown to be mainly MCHR1-specific. This data strongly indicates MCHR1 expression in rodent BAT and moreover, a peripheral, anti-obesity effect of MCHR1 antagonists directly exerted in BAT is proposed. Moreover, MCHR1 expression in murine brown adipocytes was confirmed by protein and mRNA analysis. We conclude that MCHR1 PET imaging contributes to basic research in endocrinology by elucidating the involvement of the MCH system in peripheral tissues, such as BAT.
- Published
- 2019
41. SUN-119 Melatonin Increases 3T3-L1 Adipogenesis and Brown Adipocyte Characteristics
- Author
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Tristan Cavazos, Valeria Gonzalez, Lucas Albino-Montoya, Masoud Zarei, Saraswathy Nair, Ednia Gutierrez, and Roman Sanchez_Martinez
- Subjects
medicine.medical_specialty ,endocrine system ,Adipose Tissue, Appetite, and Obesity ,Chemistry ,Brown Adipocytes ,Endocrinology, Diabetes and Metabolism ,3T3-L1 ,Melatonin ,Endocrinology ,Adipogenesis ,Internal medicine ,medicine ,Impact of Obesity on Metabolic Target Organs ,medicine.drug - Abstract
Currently, mechanisms that promote the transformation from energy storing white adipose tissue (WAT) to energy expending brown adipose tissue (BAT) are being investigated. Melatonin has been a recent target for the enhancement of BAT in other studies. The hypothesis of our investigation is that melatonin will increase adipogenesis, and white adipocytes exposed to the melatonin treatment, will be induced to develop brown adipocyte characteristics. Melatonin treatment was for 10-11 days from Day 4 of differentiation of 3T3-L1 cells. After the treatment, cells were washed with PBS, fixed with 4% paraformaldehyde and stained with Oil Red O for 1 hour, followed by hematoxylin for 2 minutes for bright field imaging microscopy for adipocytes. Live cells were stained with mitotracker for 20 min at 37°C and viewed under confocal microscopy. At day 5-6, 3T3-L1 cells treated with 1mM of melatonin had slightly increased differentiation at 19% compared to control at 13% and 10µM treated cells at 9%. At day 9-10, 1mM treated cells had 60% differentiation, 10µM treated cells 28% and control 29%. When the results were analyzed, we observed that only the differences in differentiation between control and 1mM treated cells were statistically significant for Day 9-10 (p=0.04). Data obtained also provided a comparison between big lipid (WAT like) and small lipid (BAT like) droplet formation during melatonin treatment. At Day 9-10, the quantitation of small lipid droplet containing (90%) versus big lipid droplet containing (10%) adipocytes, using bright field images for the 1mM melatonin treatment was statistically significant (p=0.002). Data obtained from oil red staining also identified that 85% of the 1mM melatonin treated adipocytes had smaller lipid droplets and 15% big lipid droplets with high statistical significance (p
- Published
- 2019
42. Brown Adipocyte and Splenocyte Co-Culture Maintains Regulatory T Cell Subset in Intermittent Hypobaric Conditions
- Author
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Tae Heung Kang, Donghyeok Shin, Jung Hwa Park, Hyungon Choi, Jeenam Kim, and Myung Chul Lee
- Subjects
CD4-Positive T-Lymphocytes ,Male ,medicine.medical_specialty ,Brown Adipocytes ,Regulatory T cell ,0206 medical engineering ,Adipocytes, White ,Biomedical Engineering ,Medicine (miscellaneous) ,Enzyme-Linked Immunosorbent Assay ,02 engineering and technology ,Brown adipocyte ,03 medical and health sciences ,Mice ,T-Lymphocyte Subsets ,Internal medicine ,medicine ,Splenocyte ,Animals ,White Adipocytes ,Cells, Cultured ,030304 developmental biology ,0303 health sciences ,Chemistry ,Flow Cytometry ,020601 biomedical engineering ,Negative pressure ,Coculture Techniques ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Endocrinology ,Adipocytes, Brown ,Tumor necrosis factor alpha ,Original Article ,Stem cell ,Intracellular ,Spleen - Abstract
Background: Brown adipocytes have thermogenic characteristics in neonates and elicit anti-inflammatory responses. We postulated that thermogenic brown adipocytes produce distinctive intercellular effects in a hypobaric state. The purpose of this study is to analyze the correlation between brown adipocyte and regulatory T cell (Treg) expression under intermittent hypobaric conditions. Methods: Brown and white adipocytes were harvested from the interscapular and flank areas of C57BL6 mice, respectively. Adipocytes were cultured with syngeneic splenocytes after isolation and differentiation. Intermittent hypobaric conditions were generated using cyclic negative pressure application for 48 h in both groups of adipocytes. Expression levels of Tregs (CD4 + CD25 + Foxp3 + T cells), cytokines [tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10), and the programmed death-ligand 1 (PD-L1)] co-inhibitory ligand were examined. Results: Splenocytes, cultured with brown and white adipocytes, exhibited comparable Treg expression in a normobaric state. Under hypobaric conditions, brown adipocytes maintained a subset of Tregs. However, a decrease in Tregs was found in the white adipocyte group. TNF-α levels increased in both groups under hypobaric conditions. In the brown adipocyte group, anti-inflammatory IL-10 expression increased significantly; meanwhile, IL-10 expression decreased in the white adipocyte group. PD-L1 levels increased more significantly in brown adipocytes than in white adipocytes under hypobaric conditions. Conclusion: Both brown and white adipocytes support Treg expression when they are cultured with splenocytes. Of note, brown adipocytes maintained Treg expression in intermittent hypobaric conditions. Anti-inflammatory cytokines and co-inhibitory ligands mediate the immunomodulatory effects of brown adipocytes under altered atmospheric conditions. Brown adipocytes showed the feasibility as a source of adjustment in physical stresses.
- Published
- 2019
43. Brown adipose tissue: a new human organ?
- Author
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Helen Budge, Michael E. Symonds, Shalini Ojha, and M Birtwistle
- Subjects
medicine.medical_specialty ,Brown Adipocytes ,Endocrinology, Diabetes and Metabolism ,Adipose tissue ,Biology ,Carbohydrate metabolism ,medicine.disease ,Obesity ,medicine.anatomical_structure ,Endocrinology ,Total energy expenditure ,Internal medicine ,Brown adipose tissue ,medicine ,Thermogenesis ,Lipoprotein - Abstract
Metabolism & Endocrinology Themed Meeting of the Physiological Society. Brown adipose tissue: a new human organ? The Royal Society, London, UK, 11-13 December 2012 The prevalence of obesity and overweight is increasing rapidly and functional brown adipose tissue (BAT), with its role in energy expenditure, may provide one solution. However, several key questions remain: what is the role of BAT in body metabolism, does substantial diet-induced thermogenesis exist in BAT and can it have a significant impact on total energy expenditure? Brown adipocytes are present within white adipose depots (BRITE cells) and the transcriptional control of these and classical brown adipocytes, remains an area of immense research interest. In addition, BAT has a role in lipoprotein and glucose metabolism and may play a part in aging. These, and several other burning issues around BAT, were discussed at a meeting of the Physiological Society in London, UK (11-13 December 2012).
- Published
- 2019
44. Environmental Pollutants Effect on Brown Adipose Tissue
- Author
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Gaetana Paolella, Mario Alberto Burgos Aceves, Lillà Lionetti, Marilena Lepretti, Rosa Anna Busiello, and Ilaria Di Gregorio
- Subjects
0301 basic medicine ,brown adipocytes ,obesity ,medicine.medical_specialty ,Physiology ,Mini Review ,perfluorooctanoic acid (PFOA) ,Adipose tissue ,030209 endocrinology & metabolism ,Biology ,dichlorodiphenylethylene (DDE) ,lcsh:Physiology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Insulin resistance ,Physiology (medical) ,Internal medicine ,Brown adipose tissue ,medicine ,metabolic disorders ,air pollutants ,dichlorodiphenyltrichoroethane (DDT) ,perfluorooctane sulfonate (PFOS) ,Pollutant ,lcsh:QP1-981 ,medicine.disease ,Thermogenin ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Perfluorooctanoic acid ,Metabolic syndrome ,Thermogenesis - Abstract
Brown adipose tissue (BAT) with its thermogenic function due to the presence of the mitochondrial uncoupling protein 1 (UCP1), has been positively associated with improved resistance to obesity and metabolic diseases. During recent years, the potential influence of environmental pollutants on energetic homoeostasis and obesity development has drawn increased attention. The purpose of this review is to discuss how regulation of BAT function could be involved in the environmental pollutant effect on body energy metabolism. We mainly focused in reviewing studies on animal models, which provide a better insight into the cellular mechanisms involved in this effect on body energy metabolism. The current literature supports the hypothesis that some environmental pollutants, acting as endocrine disruptors (EDCs), such as dichlorodiphenyltrichoroethane (DDT) and its metabolite dichlorodiphenylethylene (DDE) as well as some, traffic pollutants, are associated with increased obesity risk, whereas some other chemicals, such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), had a reverse association with obesity. Noteworthy, the EDCs associated with obesity and metabolic disorders impaired BAT mass and function. Perinatal exposure to DDT impaired BAT thermogenesis and substrate utilization, increasing susceptibility to metabolic syndrome. Ambient particulate air pollutions induced insulin resistance associated with BAT mitochondrial dysfunction. On the other hand, the environmental pollutants (PFOS/PFOA) elicited a reduction in body weight and adipose mass associated with upregulation of UCP1 and increased oxidative capacity in brown-fat mitochondria. Further research is needed to better understand the physiological role of BAT in response to exposure to both obesogenic and anti-obesogenic pollutants and to confirm the same role in humans.
- Published
- 2019
45. Brown Adipose Tissue—A Therapeutic Target in Obesity?
- Author
-
Paul Trayhurn
- Subjects
0301 basic medicine ,Opinion ,obesity ,medicine.medical_specialty ,Physiology ,Brown Adipocytes ,lcsh:Physiology ,03 medical and health sciences ,Physiology (medical) ,Internal medicine ,Brown adipose tissue ,medicine ,lcsh:QP1-981 ,Chemistry ,thermogenesis ,Beige Adipocytes ,medicine.disease ,beige adipocyte ,Obesity ,Thermogenin ,uncoupling protein-1 ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,brown adipocyte ,Thermogenesis - Published
- 2018
46. Potential novel therapeutic strategies from understanding adipocyte transdifferentiation mechanisms
- Author
-
Andrea Frontini and Loris Sartini
- Subjects
medicine.medical_specialty ,Cell type ,Brown Adipocytes ,Endocrinology, Diabetes and Metabolism ,Transdifferentiation ,Biology ,Thermogenin ,Cell biology ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Internal medicine ,Adipocyte ,Brite Adipocytes ,medicine ,White Adipocytes ,Gene - Abstract
Brown adipocytes are located in discrete anatomical locations in both small mammals and in humans. 'Brown-like' adipocytes, also known as brite (brown in white) or beige adipocytes are found interspersed among white adipocytes in several fat depots. From a functional point of view, the activity of brown and brite cells is similar, that is, heat production mediated by uncoupling protein 1. The morphology and expression of 'thermogenic' genes is also very similar in these two cell types. The origin of brite adipocytes is under intense investigation because enhancing their presence and activity has the potential to promote a healthy metabolic profile. Transdifferentiation mechanisms as well as de novo recruitment have been investigated. The characterization of the mechanisms involved in the recruitment and activation of brown/brite adipocytes in adult humans, could open the avenue for promising therapeutic strategies to curb metabolic diseases.
- Published
- 2018
47. Effect of glucocorticoids on the activity, expression and proximal promoter of type II deiodinase in rat brown adipocytes
- Author
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María Jesús Obregón, Rosa-Maria Calvo, Laura Sanchez Garcia, Raquel Martinez-deMena, Comunidad de Madrid, Instituto de Salud Carlos III, Ministerio de Educación y Ciencia (España), Ministerio de Ciencia e Innovación (España), and Ministerio de Economía y Competitividad (España)
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Hydrocortisone ,Deiodinase ,Response element ,DIO2 ,030209 endocrinology & metabolism ,Biology ,Iodide Peroxidase ,Biochemistry ,Dexamethasone ,Gene Expression Regulation, Enzymologic ,Rats, Sprague-Dawley ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Adipocyte ,Internal medicine ,Brown adipose tissue ,medicine ,Animals ,RNA, Messenger ,Promoter Regions, Genetic ,Glucocorticoids ,Molecular Biology ,Cells, Cultured ,Uncoupling Protein 1 ,Triiodothyronine ,Brown adipocytes ,Type 2 deiodinase DIO2 ,Adipocytes, Brown ,Phenotype ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Lipogenesis ,biology.protein ,Thermogenesis ,hormones, hormone substitutes, and hormone antagonists ,Half-Life - Abstract
Triiodothyronine (T3) is important for thermogenesis in brown adipose tissue (BAT). Type II deiodinase (DIO2) produces T3 required for intracellular needs in BAT. Brown adipocytes in culture require T3 for the adrenergic stimulation of DIO2. Glucocorticoids induce adipocyte differentiation (lipogenesis). We investigated the regulation of DIO2 activity, Dio2 mRNA and Dio2 promoter activity by glucocorticoids in primary cultures of rat brown adipocytes using dexamethasone (DEX) and hydrocortisone (HC). DEX and HC regulated the adrenergic stimulation of DIO2 activity in a dose- and time-dependent manner, inhibiting DIO2 activity at short treatment times and large doses (1-10 μM) and stimulating DIO2 at low HC doses (1-100 nM) and longer times (DEX). Insulin depletion reduced DIO2 activity but the response to glucocorticoids remained unchanged. DEX and HC inhibited basal DIO2 activity. DEX had no effect on DIO2 half-life, whereas HC stabilized DIO2 activity. DEX and HC inhibited the adrenergic stimulation of Dio2 mRNA expression (100-10000 nM, 14-96 h), but stabilized Dio2 mRNA, particularly DEX. DEX increased basal Dio2 mRNA levels, possibly through stabilization of Dio2 mRNA. An 807 bp construct of the murine Dio2 proximal promoter showed maximal reporter activity, with the cAMP response element (CRE) essential for transcriptional activity. DEX caused inhibition in most constructs containing the CRE element whereas HC stimulated reporter activity in the 807 bp construct. Glucocorticoids inhibited the adrenergic stimulation of Dio2 at the transcriptional level in brown adipocytes, although DIO2 activity increased with HC, possibly due to stabilization of Dio2 activity and mRNA. The CRE and cEBP elements of the Dio2 promoter seem involved in the regulation by glucocorticoids., This work was supported by research grants FISS 99/0813 from Fondo de Investigaciones Sanitarias (FIS), CAM S2010/BMD-2423 from Comunidad de Madrid (CAM) (Spain), SAF2006-01319 from MEC, SAF2009-09364 from MICINN and SAF2012-32491 from MINECO all to MJO.
- Published
- 2016
48. The Effects of High Fat Diet and Resveratrol on Mitochondrial Activity of Brown Adipocytes
- Author
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Eun Jig Lee, Zhen Yu Hong, Yoon Hee Cho, Seung Soo Hong, Ha Lee, Sue Ji Lee, and Cheol Ryong Ku
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Letter ,Brown Adipocytes ,viruses ,Endocrinology, Diabetes and Metabolism ,Mitochondrion ,Resveratrol ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,03 medical and health sciences ,chemistry.chemical_compound ,Adipocytes, brown ,Endocrinology ,Diabetes mellitus ,Internal medicine ,Brown adipose tissue ,medicine ,Endocrine Research ,chemistry.chemical_classification ,lcsh:RC648-665 ,business.industry ,Phytoalexin ,Diet, high-fat ,virus diseases ,food and beverages ,High fat diet ,respiratory system ,medicine.disease ,Obesity ,Mitochondria ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Estrogen receptor alpha ,Original Article ,business - Abstract
Background Resveratrol (RSV) is a polyphenolic phytoalexin that has many effects on metabolic diseases such as diabetes and obesity. Given the importance of brown adipose tissue (BAT) for energy expenditure, we investigated the effects of RSV on brown adipocytes. Methods For the in vitro study, interscapular BAT was isolated from 7-week-old male Sprague Dawley rats. For the in vivo study, 7-week-old male Otsuka Long Evans Tokushima Fatty (OLETF) rats were divided into four groups and treated for 27 weeks with: standard diet (SD); SD+RSV (10 mg/kg body weight, daily); high fat diet (HFD); HFD+RSV. RSV was provided via oral gavage once daily during the in vivo experiments. Results RSV treatment of primary cultured brown preadipocytes promoted mitochondrial activity, along with over-expression of estrogen receptor α (ER-α). In OLETF rats, both HFD and RSV treatment increased the weight of BAT and the differentiation of BAT. However, only RSV increased the mitochondrial activity and ER-α expression of BAT in the HFD-fed group. Finally, RSV improved the insulin sensitivity of OLETF rats by increasing the mitochondrial activity of BAT, despite having no effects on white adipocytes and muscles in either diet group. Conclusion RSV could improve insulin resistance, which might be associated with mitochondrial activity of brown adipocyte. Further studies evaluating the activity of RSV for both the differentiation and mitochondrial activity of BAT could be helpful in investigating the effects of RSV on metabolic parameters.
- Published
- 2016
49. Searching for Classical Brown Fat in Humans: Development of a Novel Human Fetal Brown Stem Cell Model
- Author
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Roberta Squecco, Gianni Forti, Gabriella B. Vannelli, Daniele Guasti, Benedetta Mazzanti, Eglantina Idrizaj, Michaela Luconi, José M. Gallego-Escuredo, Alessandra Di Franco, Daniele Bani, Francesc Villarroya, and Francesca Rossi
- Subjects
Adult ,0301 basic medicine ,medicine.medical_specialty ,Cellular differentiation ,UCP-1 ,Cell ,Adipose tissue ,030209 endocrinology & metabolism ,Cell Separation ,Stem cells ,Biology ,Models, Biological ,03 medical and health sciences ,0302 clinical medicine ,Adipose Tissue, Brown ,Internal medicine ,Brown adipose tissue ,medicine ,Humans ,Cell Lineage ,Fetal Stem Cells ,Adipogenesis ,Brown adipocytes ,Mesenchymal stem cell ,Cell Differentiation ,Mesenchymal Stem Cells ,Cell Biology ,Electrophysiological Phenomena ,Organoids ,Adipocytes, Brown ,Phenotype ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Thermography ,Molecular Medicine ,Cell electrophysiology ,Stem cell ,Developmental Biology - Abstract
The potential therapeutic applications of targeting brown adipose tissue open new clinical avenues in fighting against metabolic pathologies. However, due to the limited extension in adult humans of brown depots, which are dramatically reduced after birth, solid cell models to study human brown adipogenesis and its regulatory factors in pathophysiology are urgently needed. Here, we generated a novel human model of brown adipose stem cells, hfB-ASC, derived for the first time from fetal interscapular brown fat depots. Besides the characterization of their stem and classical brown adipose properties, we demonstrated that these cells retain a specific intrinsic differentiation program to functional brown adipocytes, even spontaneously generating organoid structures with brown features. Moreover, for the first time, we investigated the thermogenic and electrophysiological activity of the in vitro-derived fetal brown adipocytes compared to their undifferentiated precursors hfB-ASC, in basal and norepinephrine-induced conditions. In conclusion, from interscapular brown fat of the human fetus we developed and functionally characterized a novel physiological brown adipose stem cell model early programmed to brown differentiation, which may represent a unique opportunity for further studies on brown adipogenesis processes in humans as well as the most suitable target to study novel therapeutic approaches for stimulating brown activity in metabolic pathologies.
- Published
- 2016
50. Cyclooxygenase 2 Regulates Isoprenaline Induced Adipolysis In Brown Adipocytes
- Author
-
Rongxin Zhu, Lijing Gong, and Guang Cai
- Subjects
medicine.medical_specialty ,Adipolysis ,biology ,Brown Adipocytes ,Chemistry ,Physical Therapy, Sports Therapy and Rehabilitation ,Endocrinology ,Internal medicine ,Isoprenaline ,medicine ,biology.protein ,Orthopedics and Sports Medicine ,Cyclooxygenase ,medicine.drug - Published
- 2020
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