20,578 results on '"brown adipose tissue"'
Search Results
2. Effect of Glyceroltrinitrate on Human Energy Expenditure and Brown Adipose Tissue Thermogenesis (NEXT)
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- 2024
3. Winter-Swimming and Brown Adipose Tissue Activity in Middel-aged Obese Subjects (WinterBAT). (WinterBAT)
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Kristian Karstoft, MD, PhD, Chief Physician
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- 2024
4. MIrabegron and Physiological Function in Cold Environments
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Office of Naval Research (ONR) and Blair D. Johnson, PhD, Associate Professor School of Public Health
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- 2024
5. Sympathetic innervation of interscapular brown adipose tissue is not a predominant mediator of oxytocin-elicited reductions of body weight and adiposity in male diet-induced obese mice
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Edwards, Melise M, Nguyen, Ha K, Dodson, Andrew D, Herbertson, Adam J, Wolden-Hanson, Tami, Wietecha, Tomasz A, Honeycutt, Mackenzie K, Slattery, Jared D, O’Brien, Kevin D, Graham, James L, Havel, Peter J, Mundinger, Thomas O, Sikkema, Carl L, Peskind, Elaine R, Ryu, Vitaly, Taborsky, Gerald J, and Blevins, James E
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Medical Physiology ,Biomedical and Clinical Sciences ,Obesity ,Neurosciences ,Nutrition ,Metabolic and endocrine ,Animals ,Oxytocin ,Adipose Tissue ,Brown ,Male ,Mice ,Sympathetic Nervous System ,Diet ,High-Fat ,Adiposity ,Mice ,Inbred C57BL ,Body Weight ,Weight Loss ,Mice ,Obese ,Energy Metabolism ,Norepinephrine ,obesity ,brown adipose tissue ,white adipose tissue ,oxytocin ,food intake ,Clinical Sciences ,Nutrition and Dietetics ,Clinical sciences - Abstract
Previous studies indicate that CNS administration of oxytocin (OT) reduces body weight in high fat diet-induced obese (DIO) rodents by reducing food intake and increasing energy expenditure (EE). We recently demonstrated that hindbrain (fourth ventricular [4V]) administration of OT elicits weight loss and elevates interscapular brown adipose tissue temperature (TIBAT, a surrogate measure of increased EE) in DIO mice. What remains unclear is whether OT-elicited weight loss requires increased sympathetic nervous system (SNS) outflow to IBAT. We hypothesized that OT-induced stimulation of SNS outflow to IBAT contributes to its ability to activate BAT and elicit weight loss in DIO mice. To test this hypothesis, we determined the effect of disrupting SNS activation of IBAT on the ability of 4V OT administration to increase TIBAT and elicit weight loss in DIO mice. We first determined whether bilateral surgical SNS denervation to IBAT was successful as noted by ≥ 60% reduction in IBAT norepinephrine (NE) content in DIO mice. NE content was selectively reduced in IBAT at 1-, 6- and 7-weeks post-denervation by 95.9 ± 2.0, 77.4 ± 12.7 and 93.6 ± 4.6% (P
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- 2024
6. Brown adipose tissue CoQ deficiency activates the integrated stress response and FGF21-dependent mitohormesis.
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Chang, Ching-Fang, Gunawan, Amanda, Liparulo, Irene, Zushin, Peter-James, Vitangcol, Kaitlyn, Timblin, Greg, Saijo, Kaoru, Wang, Biao, Parlakgül, Güneş, Arruda, Ana, and Stahl, Andreas
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Brown Adipose Tissue ,Coenzyme Q ,FGF21 ,Mitochondrial Unfolded Protein Response ,Mitohormesis ,Animals ,Mice ,Adipose Tissue ,Brown ,Ubiquinone ,Mitochondrial Diseases ,Thermogenesis ,Mice ,Inbred C57BL ,Ataxia ,Fibroblast Growth Factors ,Muscle Weakness - Abstract
Coenzyme Q (CoQ) is essential for mitochondrial respiration and required for thermogenic activity in brown adipose tissues (BAT). CoQ deficiency leads to a wide range of pathological manifestations, but mechanistic consequences of CoQ deficiency in specific tissues, such as BAT, remain poorly understood. Here, we show that pharmacological or genetic CoQ deficiency in BAT leads to stress signals causing accumulation of cytosolic mitochondrial RNAs and activation of the eIF2α kinase PKR, resulting in activation of the integrated stress response (ISR) with suppression of UCP1 but induction of FGF21 expression. Strikingly, despite diminished UCP1 levels, BAT CoQ deficiency displays increased whole-body metabolic rates at room temperature and thermoneutrality resulting in decreased weight gain on high-fat diets (HFD). In line with enhanced metabolic rates, BAT and inguinal white adipose tissue (iWAT) interorgan crosstalk caused increased browning of iWAT in BAT-specific CoQ deficient animals. This mitohormesis-like effect depends on the ATF4-FGF21 axis and BAT-secreted FGF21, revealing an unexpected role for CoQ in the modulation of whole-body energy expenditure with wide-ranging implications for primary and secondary CoQ deficiencies.
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- 2024
7. Brown Fat Activation and Browning Efficiency Augmented by Chronic Cold and Nutraceuticals for Brown Adipose Tissue-mediated Effect Against Metabolic Syndrome (BEACON BEAMS Study)
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Duke-NUS Graduate Medical School, Canadian Imaging Research Centre (CIRC), National University of Singapore, Singapore Institute of Food and Biotechnology Innovation (SIFBI), Singapore Bioimaging Consortium (SBIC), and Melvin Leow, Principal Investigator
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- 2024
8. Enrichment of novel CD3+F4/80 + cells in brown adipose tissue following adrenergic stimulation.
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Hee-Don Chae and Levi, Jelena
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Macrophages play a multifaceted role in maintaining tissue homeostasis, fighting infections, and regulating cold-induced thermogenesis. The brown adipose tissue (BAT) is crucial for maintaining body temperature during cold exposure. Cold stress triggers the sympathetic nervous system to release norepinephrine (NE), which activates BAT via β3-adrenergic receptors, initiating lipolysis and glycolysis. BAT-infiltrating macrophages can either hinder or enhance thermogenesis by controlling the interplay between BAT cells and sympathetic nerves. In this study we report on a unique population of CD3+F4/80+ dual lineage co-expressing (DE) cells within the interscapular BAT (iBAT), that increased following chronic adrenergic stimulation. In forward scatter/side scatter plots, they formed a cluster distinct from lymphocytes, appearing larger and more complex. These CD3+F4/80+ DE cells demonstrated the lack of T cell markers CD62L and TCRβ and expressed higher levels of Ly6C, F4/80, and CD11b markers compared to T cells and CD3- macrophages. Furthermore, analysis revealed two subpopulations within the CD3+F4/80+ DE population based on MHCII expression, with the proportion of MHCII-low subset increasing with adrenergic stimulation. This novel DE population within iBAT, unequivocally identified by the its unique surface marker profile, warrants further investigation into the intricate mechanisms governing adaptive thermogenesis regulation. [ABSTRACT FROM AUTHOR]
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- 2024
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9. Brown Adipose Tissue Activity and Childhood Exposure to Cold Are Associated With Hot Flashes at Menopause.
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Sievert, Lynnette Leidy, Shreyer, Sofiya, Witkowski, Sarah, and Brown, Daniel E.
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BROWN adipose tissue , *HOT flashes , *SKIN temperature , *LOGISTIC regression analysis , *THERMOGRAPHY , *BATS - Abstract
ABSTRACT Objective Methods Results Conclusion Hot flashes (HFs) are experienced as sudden sensations of heat. We hypothesized that brown adipose tissue (BAT) activation could increase the likelihood of HFs in winter. The aim of this study was to test whether women with more BAT activity were more likely to experience self‐reported or biometrically measured HFs.Women aged 45–55 years (n = 270) participated in face‐to‐face interviews and anthropometric and ambulatory measures. Level of BAT activity was estimated from the difference in supraclavicular skin temperature measured by infrared thermography before and after cooling. Logistic regressions were applied to examine whether bothersome HFs (yes/no) during the past 2 weeks were associated with BAT activity, adjusting for menopausal status, childhood exposure to cold, waist/hip ratio, and self‐reported health. Linear regressions were used to examine the frequency of self‐reported and biometrically measured HFs during the study period and BAT activity, adjusting for potential confounders.Menopausal status, childhood exposure to cold, waist‐to‐hip ratio (WHR), and self‐reported health were associated with both BAT activity and HFs. After adjusting for potential confounders, an increase in BAT activity almost tripled the likelihood of bothersome HFs (OR 2.84, 95% CI 1.26–6.43). In linear regressions, BAT activity was not associated with frequency of subjective or objective HFs during the study period, but childhood exposure to cold was associated with subjective HF report (β = 0.163, p = 0.010).To our knowledge, this is the first study of BAT activation and HFs. Our results support a role for BAT activity in HF experience. Therefore, we encourage further examination of the role of BAT, as well as childhood exposure to cold, in HFs. [ABSTRACT FROM AUTHOR]
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- 2024
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10. Triiodothyronine (T3) promotes browning of white adipose through inhibition of the PI3K/AKT signalling pathway.
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Huang, LingHong, Guo, ZhiFeng, Huang, MingJing, Zeng, XiYing, and Huang, HuiBin
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PI3K/AKT pathway , *CELLULAR signal transduction , *WHITE adipose tissue , *ADIPOGENESIS , *TRIIODOTHYRONINE , *BROWN adipose tissue , *THYROID hormone receptors - Abstract
Obesity arises from an imbalance between energy consumption and energy expenditure, and thyroid hormone levels serve as a determinant of energy expenditure. We conducted experiments at the animal and cellular levels and combined those findings with clinical data to elucidate the role of triiodothyronine (T3) in facilitating the browning of white adipose tissue (WAT) and its underlying mechanism. The results showed (i) the impaired metabolic function of local WAT and the compensatory elevation of systemic thermogenesis in obesity; (ii) T3 treatment of white adipocytes in vitro and local WAT in vivo induced a shift towards a morphologically "brown" phenotype, accompanied by upregulation of mRNA and protein expression of browning-related and mitochondrial function markers, which suggest that T3 intervention promotes the browning of WAT; and (iii) the aforementioned processes could be modulated through inhibition of the PI3K/AKT signalling pathway; however, whether T3 affects the PI3K/AKT signalling pathway by affecting insulin signalling remains to be studied and clarified. The results of our study indicate that T3 treatment promotes browning of WAT through inhibition of the PI3K/AKT signalling pathway; these findings offer novel perspectives regarding the potential of localised therapies for addressing WAT volume in individuals with obesity. [ABSTRACT FROM AUTHOR]
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- 2024
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11. Comparative functional analysis reveals differential nucleotide sensitivity between human and mouse UCP1.
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Musiol, Eva, Fromme, Tobias, Hau, Julia, Di Pizio, Antonella, and Klingenspor, Martin
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BROWN adipose tissue , *PURINE nucleotides , *FREE fatty acids , *UNCOUPLING proteins , *ADIPOSE tissues - Abstract
Aim: Mitochondrial uncoupling protein 1 (UCP1) is a unique protein of brown adipose tissue. Upon activation by free fatty acids, UCP1 facilitates a thermogenic net proton flux across the mitochondrial inner membrane. Non‐complexed purine nucleotides inhibit this fatty acid‐induced activity of UCP1. The most available data have been generated from rodent model systems. In light of its role as a putative pharmacological target for treating metabolic disease, in‐depth analyses of human UCP1 activity, regulation, and structural features are essential. Methods: In the present study, we established a doxycycline‐regulated cell model with inducible human or murine UCP1 expression and conducted functional studies using respirometry comparing wild‐type and mutant variants of human UCP1. Results: We demonstrate that human and mouse UCP1 exhibit similar specific fatty acid‐induced activity but a different inhibitory potential of purine nucleotides. Mutagenesis of non‐conserved residues in human UCP1 revealed structural components in α‐helix 56 and α‐helix 6 crucial for uncoupling function. Conclusion: Comparative studies of human UCP1 with other orthologs can provide new insights into the structure–function relationship for this mitochondrial carrier and will be instrumental in searching for new activators. [ABSTRACT FROM AUTHOR]
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- 2024
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12. Neuregulin4‐ErbB4 signalling pathway is driven by electroacupuncture stimulation to remodel brown adipose tissue innervation.
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Yu, Ziwei, Zhang, Ting, Yang, Xingyu, Xu, Bin, Yu, Zhi, An, Li, Xu, Tiancheng, Jing, Xinyue, Wang, Yaling, and Lu, Mengjiang
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BROWN adipose tissue , *SYMPATHETIC nervous system , *CENTRAL nervous system , *BIOTRANSFORMATION (Metabolism) , *LABORATORY mice , *HYPOTHALAMUS - Abstract
Aim: To show that electroacupuncture stimulation (ES) remodels sympathetic innervation in brown adipose tissue (BAT) via the bone morphogenic protein 8B (BMP8B)‐neuregulin 4 (NRG4)‐ErbB4 axis, with somatotopic dependence. Materials and methods: We established a high‐fat diet (HFD) model with C57BL/6J mice to measure the thermogenesis and metabolism of BAT. In addition, the sympathetic nerve activity (SNA) was measured with the electrophysiological technique, and the immunostaining of c‐Fos was used to detect the central nervous system sources of sympathetic outflows. Finally, the key role of the BMP8B‐NRG4‐ErbB4 axis was verified by peripheral specific antagonism of ErbB4. Results: ES at the forelimb and abdomen regions significantly up‐regulate SNA, whereas ES at the hindlimb region has a limited regulatory effect on SNA but still partially restores HFD‐induced BAT dysfunction. Mechanistically, ES at the forelimb and abdomen regions driving catecholaminergic signals in brown adipocytes depends on neural activities projected from the ventromedial nucleus of the hypothalamus (VMH) to the spinal cord intermediolateral column (IML). Notably, the peripheral suppression of ErbB4 in BAT inhibits the thermogenesis and metabolic function of BAT, as well as significantly hindering the SNA activation and metabolic benefits induced by ES. Conclusion: These results suggest that ES appears to be an effective approach for remodeling sympathetic innervation in BAT, which is closely related to neuronal activity in the VMH and the NRG4‐ErbB4 signaling pathway. [ABSTRACT FROM AUTHOR]
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- 2024
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13. Kinin B1 receptor deficiency promotes enhanced adipose tissue thermogenic response to β3-adrenergic stimulation.
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Branquinho, Jéssica, Neves, Raquel L., Martin, Renan P., Arata, Júlia G., Bittencourt, Clarissa A., Araújo, Ronaldo C., Icimoto, Marcelo Y., and Pesquero, João B.
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WHITE adipose tissue , *BROWN adipose tissue , *METABOLIC regulation , *KREBS cycle , *ADIPOSE tissues - Abstract
Objective and design: Kinin B1 receptor (B1R) has a key role in adipocytes to protect against obesity and glycemic metabolism, thus becoming a potential target for regulation of energy metabolism and adipose tissue thermogenesis. Material or subjects: Kinin B1 knockout mice (B1KO) were subjected to acute induction with CL 316,243 and chronic cold exposure. Methods: Metabolic and histological analyses, gene and protein expression and RNA-seq were performed on interscapular brown adipose tissue (iBAT) and inguinal white adipose tissue (iWAT) of mice. Results: B1KO mice, under acute effect of CL 316,243, exhibited increased energy expenditure and upregulated thermogenic genes in iWAT. They were also protected from chronic cold, showing enhanced non-shivering thermogenesis with increased iBAT mass (~ 90%) and recruitment of beige adipocytes in iWAT (~ 50%). Positive modulation of thermogenic and electron transport chain genes, reaching a 14.5-fold increase for Ucp1 in iWAT. RNA-seq revealed activation of the insulin signaling pathways for iBAT and oxidative phosphorylation, tricarboxylic acid cycle, and browning pathways for iWAT. Conclusion: B1R deficiency induced metabolic and gene expression alterations in adipose tissue, activating thermogenic pathways and increasing energy metabolism. B1R antagonists emerge as promising therapeutic targets for regulating obesity and associated metabolic disorders, such as inflammation and diabetes. [ABSTRACT FROM AUTHOR]
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- 2024
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14. Doublecortin-like knockdown in mice attenuates obesity by stimulating energy expenditure in adipose tissue.
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Modder, Melanie, Coomans, Claudia P., Saaltink, Dirk-Jan, Tersteeg, Mayke M. H., Hoogduin, Janna, Scholten, Leonie, Pronk, Amanda C. M., Lalai, Reshma A., Boelen, Anita, Kalsbeek, Andries, Rensen, Patrick C. N., Vreugdenhil, Erno, and Kooijman, Sander
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WHITE adipose tissue , *BROWN adipose tissue , *REGULATION of body weight , *WEIGHT loss , *WEIGHT gain , *ADIPOSE tissues - Abstract
Crosstalk between peripheral metabolic organs and the central nervous system is essential for body weight control. At the base of the hypothalamus, β-tanycytes surround the portal capillaries and function as gatekeepers to facilitate transfer of substances from the circulation into the cerebrospinal fluid and vice versa. Here, we investigated the role of the neuroplasticity gene doublecortin-like (DCL), highly expressed by β-tanycytes, in body weight control and whole-body energy metabolism. We demonstrated that DCL-knockdown through a doxycycline-inducible shRNA expression system prevents body weight gain by reducing adiposity in mice. DCL-knockdown slightly increased whole-body energy expenditure possibly as a result of elevated circulating thyroid hormones. In white adipose tissue (WAT) triglyceride uptake was increased while the average adipocyte cell size was reduced. At histological level we observed clear signs of browning, and thus increased thermogenesis in WAT. We found no indications for stimulated thermogenesis in brown adipose tissue (BAT). Altogether, we demonstrate an important, though subtle, role of tanycytic DCL in body weight control through regulation of energy expenditure, and specifically WAT browning. Elucidating mechanisms underlying the role of DCL in regulating brain-peripheral crosstalk further might identify new treatment targets for obesity. [ABSTRACT FROM AUTHOR]
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- 2024
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15. Chronic β3‐AR stimulation activates distinct thermogenic mechanisms in brown and white adipose tissue and improves systemic metabolism in aged mice.
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Natarajan, Duraipandy, Plakkot, Bhuvana, Tiwari, Kritika, Ekambaram, Shoba, Wang, Weidong, Rudolph, Michael, Mohammad, Mahmoud A., Chacko, Shaji K., Subramanian, Madhan, Tarantini, Stefano, Yabluchanskiy, Andriy, Ungvari, Zoltan, Csiszar, Anna, and Balasubramanian, Priya
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WHITE adipose tissue , *FATTY acid oxidation , *BROWN adipose tissue , *METABOLIC disorders , *ADRENERGIC agonists - Abstract
Adipose thermogenesis has been actively investigated as a therapeutic target for improving metabolic dysfunction in obesity. However, its applicability to middle‐aged and older populations, which bear the highest obesity prevalence in the United States (approximately 40%), remains uncertain due to age‐related decline in thermogenic responses. In this study, we investigated the effects of chronic thermogenic stimulation using the β3‐adrenergic (AR) agonist CL316,243 (CL) on systemic metabolism and adipose function in aged (18‐month‐old) C57BL/6JN mice. Sustained β3‐AR treatment resulted in reduced fat mass, increased energy expenditure, increased fatty acid oxidation and mitochondrial activity in adipose depots, improved glucose homeostasis, and a favorable adipokine profile. At the cellular level, CL treatment increased uncoupling protein 1 (UCP1)‐dependent thermogenesis in brown adipose tissue (BAT). However, in white adipose tissue (WAT) depots, CL treatment increased glycerol and lipid de novo lipogenesis (DNL) and turnover suggesting the activation of the futile substrate cycle of lipolysis and reesterification in a UCP1‐independent manner. Increased lipid turnover was also associated with the simultaneous upregulation of proteins involved in glycerol metabolism, fatty acid oxidation, and reesterification in WAT. Further, a dose‐dependent impact of CL treatment on inflammation was observed, particularly in subcutaneous WAT, suggesting a potential mismatch between fatty acid supply and oxidation. These findings indicate that chronic β3‐AR stimulation activates distinct cellular mechanisms that increase energy expenditure in BAT and WAT to improve systemic metabolism in aged mice. Considering that people lose BAT with aging, activation of futile lipid cycling in WAT presents a novel strategy for improving age‐related metabolic dysfunction. [ABSTRACT FROM AUTHOR]
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- 2024
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16. Association between thermogenic brown fat and genes under positive natural selection in circumpolar populations.
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Ishida, Yuka, Matsushita, Mami, Yoneshiro, Takeshi, Saito, Masayuki, and Nakayama, Kazuhiro
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EAST Asians ,SINGLE nucleotide polymorphisms ,BROWN adipose tissue ,NATURAL selection ,COLD adaptation - Abstract
Background: Adaptation to cold was essential for human migration across Eurasia. Non-shivering thermogenesis through brown adipose tissue (BAT) participates in cold adaptation because some genes involved in the differentiation and function of BAT exhibit signatures of positive natural selection in populations at high latitudes. Whether these genes are associated with the inter-individual variability in BAT thermogenesis remains unclear. In this study, we evaluated the potential associations between BAT activity and single nucleotide polymorphisms (SNPs) in candidate gene regions in East Asian populations. Methods: BAT activity induced by mild cold exposure was measured in 399 healthy Japanese men and women using fluorodeoxyglucose-positron emission tomography and computed tomography (FDG-PET/CT). The capacity for cold-induced thermogenesis and fat oxidation was measured in 56 men. Association analyses with physiological traits were performed for 11 SNPs at six loci (LEPR, ANGPTL8, PLA2G2A, PLIN1, TBX15-WARS2, and FADS1) reported to be under positive natural selection. Associations found in the FDG-PET/CT population were further validated in 84 healthy East Asian men and women, in whom BAT activity was measured using infrared thermography. Associations between the SNP genotypes and BAT activity or other related traits were tested using multiple logistic and linear regression models. Results: Of the 11 putative adaptive alleles of the six genes, two intronic SNPs in LEPR (rs1022981 and rs12405556) tended to be associated with higher BAT activity. However, these did not survive multiple test comparisons. Associations with lower body fat percentage, plasma triglyceride, insulin, and HOMA-IR levels were observed in the FDG-PET/CT population (P < 0.05). Other loci, including TBX15-WARS2, which is speculated to mediate cold adaptation in Greenland Inuits, did not show significant differences in BAT thermogenesis. Conclusions: Our results suggest a marginal but significant association between LEPR SNPs. However, robust supporting evidence was not established for the involvement of other loci under positive natural selection in cold adaptation through BAT thermogenesis in East Asian adults. Given the pleiotropic function of these genes, factors other than cold adaptation through BAT thermogenesis, such as diet adaptation, may contribute to positive natural selection at these loci. [ABSTRACT FROM AUTHOR]
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- 2024
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17. Ling-gui-zhu-gan granules reduces obesity and ameliorates metabolic disorders by inducing white adipose tissue browning in obese mice.
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Yuxiu Li, Zimengwei Ye, Yi Zhao, Bingrui Xu, Wanying Xue, Zhufeng Wang, Ran An, Fan Wang, and Rui Wu
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WHITE adipose tissue ,ADIPOSE tissues ,BROWN adipose tissue ,METABOLIC disorders ,BODY weight - Abstract
Background: Ling-gui-zhu-gan (LGZG) formula has been demonstrated to effectively ameliorate the clinical symptoms of patients with obesity or metabolic syndrome. This study aimed to explore both the effect and the underlying mechanisms of LGZG against obesity. Methods: Male C57BL/6N mice were randomized into four groups (n = 8): normal control (NC), obese (OB), metformin (Met), and LGZG. After 8 weeks of gavage administration, the pharmacological effects of LGZG on obesity and metabolism were investigated using biochemical parameters, histomorphological examination, and lipidomics techniques. Pivotal factors associated with white adipose tissue browning were evaluated using quantitative real-time polymerase chain reaction and western blotting. Results: The results revealed that LGZG reduced the levels of obesity markers, including body weights, body fat mass and food intake in obese mice. Further evaluations highlighted that LGZG restored glucose homeostasis and significantly improved insulin sensitivity in obese mice. Importantly, LGZG could adjust serum lipid profiles and regulate the lipidomic spectrum of intestinal contents, with noticeable shifts in the levels of certain lipids, particularly diacylglycerols and monoacylglycerols. Histopathological examinations of LGZG-treated mice also revealed more favorable adipose tissue structures than their obese counterparts. Furthermore, we found that LGZG upregulated the expression of several key thermogenesis-related factors, such as UCP1, PRDM16, PGC-1α, PPARα, PPARγ, CTBP1, and CTBP2 in white adipose tissues. Conclusion: Our findings position LGZG as a novel strategy for preventing obesity and improving metabolic health. [ABSTRACT FROM AUTHOR]
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- 2024
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18. ScreenDMT reveals DiHOMEs are replicably inversely associated with BMI and stimulate adipocyte calcium influx.
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Dreyfuss, Jonathan M., Djordjilović, Vera, Pan, Hui, Bussberg, Valerie, MacDonald, Allison M., Narain, Niven R., Kiebish, Michael A., Blüher, Matthias, Tseng, Yu-Hua, and Lynes, Matthew D.
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BROWN adipose tissue , *CALCIUM , *LINOLEIC acid , *FAT cells , *MATHEMATICAL proofs , *BLOOD lipids , *GLYCOLS - Abstract
Activating brown adipose tissue (BAT) improves systemic metabolism, making it a promising target for metabolic syndrome. BAT is activated by 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME), which we previously identified to be inversely associated with BMI and which directly improves metabolism in multiple tissues. Here we profile plasma lipidomics from 83 people and test which lipids' association with BMI replicates in a concordant direction using our novel tool ScreenDMT, whose power and validity we demonstrate via mathematical proofs and simulations. We find that the linoleic acid diols 12,13-diHOME and 9,10-diHOME are both replicably inversely associated with BMI and mechanistically activate calcium influx in mouse brown and white adipocytes in vitro, which implicates this signaling pathway and 9,10-diHOME as candidate therapeutic targets. ScreenDMT can be applied to test directional mediation, directional replication, and qualitative interactions, such as identifying biomarkers whose association is shared (replication) or opposite (qualitative interaction) across diverse populations. A study of blood lipids in two cohorts using a new replication test, ScreenDMT, finds that people with lower BMI have higher levels of linoleic acid diols 12,13-diHOME and 9,10-diHOME, which upregulate adipocyte calcium influx. [ABSTRACT FROM AUTHOR]
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- 2024
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19. Identification of regulatory networks and crosstalk factors in brown adipose tissue and liver of a cold-exposed cardiometabolic mouse model.
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Amor, Melina, Diaz, Malena, Bianco, Valentina, Svecla, Monika, Schwarz, Birgit, Rainer, Silvia, Pirchheim, Anita, Schooltink, Laszlo, Mukherjee, Suravi, Grabner, Gernot F., Beretta, Giangiacomo, Lamina, Claudia, Norata, Giuseppe Danilo, Hackl, Hubert, and Kratky, Dagmar
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BROWN adipose tissue , *ADIPOSE tissue diseases , *HEART metabolism disorders , *TRANSCRIPTION factors , *ENERGY metabolism , *HIGH cholesterol diet , *WESTERN diet - Abstract
Background: Activation of brown adipose tissue (BAT) has gained attention due to its ability to dissipate energy and counteract cardiometabolic diseases (CMDs). Methods: This study investigated the consequences of cold exposure on the BAT and liver proteomes of an established CMD mouse model based on LDL receptor-deficient (LdlrKO) mice fed a high-fat, high-sucrose, high-cholesterol diet for 16 weeks. We analyzed energy metabolism in vivo and performed untargeted proteomics on BAT and liver of LdlrKO mice maintained at 22 °C or 5 °C for 7 days. Results: We identified several dysregulated pathways, miRNAs, and transcription factors in BAT and liver of cold-exposed Ldlrko mice that have not been previously described in this context. Networks of regulatory interactions based on shared downstream targets and analysis of ligand-receptor pairs identified fibrinogen alpha chain (FGA) and fibronectin 1 (FN1) as potential crosstalk factors between BAT and liver in response to cold exposure. Importantly, genetic variations in the genes encoding FGA and FN1 have been associated with cardiometabolic-related phenotypes and traits in humans. Discussion: This study describes the key factors, pathways, and regulatory networks involved in the crosstalk between BAT and the liver in a cold-exposed CMD mouse model. These findings may provide a basis for future studies aimed at testing whether molecular mediators, as well as regulatory and signaling mechanisms involved in tissue adaption upon cold exposure, could represent a target in cardiometabolic disorders. [ABSTRACT FROM AUTHOR]
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- 2024
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20. Lesson on obesity and anatomy of adipose tissue: new models of study in the era of clinical and translational research.
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Luca, Tonia, Pezzino, Salvatore, Puleo, Stefano, and Castorina, Sergio
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BROWN adipose tissue , *FAT cells , *SCIENCE education , *ADIPOSE tissues , *PREVENTION of obesity - Abstract
Obesity is a serious global illness that is frequently associated with metabolic syndrome. Adipocytes are the typical cells of adipose organ, which is composed of at least two different tissues, white and brown adipose tissue. They functionally cooperate, interconverting each other under physiological conditions, but differ in their anatomy, physiology, and endocrine functions. Different cellular models have been proposed to study adipose tissue in vitro. They are also useful for elucidating the mechanisms that are responsible for a pathological condition, such as obesity, and for testing therapeutic strategies. Each cell model has its own characteristics, culture conditions, advantages and disadvantages. The choice of one model rather than another depends on the specific study the researcher is conducting. In recent decades, three-dimensional cultures, such as adipose spheroids, have become very attractive because they more closely resemble the phenotype of freshly isolated cells. The use of such models has developed in parallel with the evolution of translational research, an interdisciplinary branch of the biomedical field, which aims to learn a scientific translational approach to improve human health and longevity. The focus of the present review is on the growing body of data linking the use of new cell models and the spread of translational research. Also, we discuss the possibility, for the future, to employ new three-dimensional adipose tissue cell models to promote the transition from benchside to bedsite and vice versa, allowing translational research to become routine, with the final goal of obtaining clinical benefits in the prevention and treatment of obesity and related disorders. [ABSTRACT FROM AUTHOR]
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- 2024
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21. Neuronostatin regulates proliferation and differentiation of rat brown primary preadipocytes.
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Krążek, Małgorzata, Wojciechowicz, Tatiana, Fiedorowicz, Joanna, Strowski, Mathias Z., Nowak, Krzysztof W., and Skrzypski, Marek
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BROWN adipose tissue , *RATTUS norvegicus , *SOMATOSTATIN , *FAT cells , *CELLULAR signal transduction - Abstract
Neuronostatin suppresses the differentiation of white preadipocytes. However, the role of neuronostatin in brown adipose tissue remains elusive. Therefore, we investigated the impact of neuronostatin on the proliferation and differentiation of isolated rat brown preadipocytes. We report that neuronostatin and its receptor (GPR107) are synthesized in brown preadipocytes and brown adipose tissue. Furthermore, neuronostatin promotes the replication of brown preadipocytes via the AKT pathway. Notably, neuronostatin suppresses the expression of markers associated with brown adipogenesis (PGC‐1α, PPARγ, PRDM16, and UCP1) and reduces cellular mitochondria content. Moreover, neuronostatin impedes the differentiation of preadipocytes by activating the JNK signaling pathway. These effects were not mimicked by somatostatin. Our results suggest that neuronostatin is involved in regulating brown adipogenesis. [ABSTRACT FROM AUTHOR]
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- 2024
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22. Adipocyte-Targeted Nanocomplex with Synergistic Photothermal and Pharmacological Effects for Combating Obesity and Related Metabolic Syndromes.
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Zhang, Yuanyuan, Zeng, Xiaojiao, Wu, Fan, Yang, Xiaopeng, Che, Tingting, Zheng, Yin, Li, Jie, Zhang, Yufei, Zhang, Xinge, and Wu, Zhongming
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WEIGHT loss , *WHITE adipose tissue , *BROWN adipose tissue , *LEAN body mass , *METABOLIC syndrome , *ADIPOSE tissues - Abstract
Obesity is a global epidemic which induces a multitude of metabolic disorders. Browning of white adipose tissue (WAT) has emerged as a promising therapeutic strategy for promoting weight loss and improving associated metabolic syndromes in people with obesity. However, current methods of inducing white adipose tissue browning have limited applicability. We developed a nanocomplex pTSL@(P+I), which is a temperature-sensitive liposome (TSL) surface-conjugated with an adipocyte-targeting peptide (p) and loaded with both browning-promoting agents (P) and photosensitizing agents (I). This nanocomplex exhibits adipocyte targeting, as well as synergistic pharmacological and photothermal properties to promote browning. pTSL@(P+I) effectively upregulates UCP1 and COX5B expression by activating the transcription axis of PPARγ/PGC1α and HSF1/PGC1α, thereby promoting white adipose tissue browning and reducing obesity. This novel nanocomplex exhibited a uniform spherical shape, with an average diameter of approximately 200 nm. Additionally, the nanocomplexes exhibited remarkable photothermal properties and biocompatibility. Further, when adipocytes were treated with pTSL@(P+I), their triglyceride content decreased remarkably and intracellular mitochondrial activity increased significantly. When applied to diet-induced obesity (DIO) mice, the nanocomplex exhibited significant efficacy, demonstrating a notable 14.4% reduction in body weight from the initial measurement, a decreased fat/lean mass ratio of 20.8%, and no statistically significant disparities (p > 0.05) in associated side effects when compared to the control group. In summary, implementation of the targeted nanocomplex pTSL@(P+I) to enhance energy expenditure by stimulating white adipose tissue browning offers a promising therapeutic approach for the treatment of obesity and related metabolic syndromes. [ABSTRACT FROM AUTHOR]
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- 2024
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23. Adipose Tissue: A Novel Target of the Incretin Axis? A Paradigm Shift in Obesity-Linked Insulin Resistance.
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De Fano, Michelantonio, Malara, Massimo, Vermigli, Cristiana, and Murdolo, Giuseppe
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GASTRIC inhibitory polypeptide , *TYPE 2 diabetes , *BROWN adipose tissue , *FAT cells , *ADIPOSE tissues - Abstract
Adipose tissue (AT) represents a plastic organ that can undergo significant remodeling in response to metabolic demands. With its numerous checkpoints, the incretin system seems to play a significant role in controlling glucose homeostasis and energy balance. The importance of the incretin hormones, namely the glucagon-like peptide-1 (GLP-1) and the glucose-dependent insulinotropic peptide (GIP), in controlling the function of adipose cells has been brought to light by recent studies. Notably, a "paradigm shift" in reevaluating the role of the incretin system in AT as a potential target to treat obesity-linked metabolic disorders resulted from the demonstration that a disruption of the GIP and GLP-1 signaling axis in fat is associated with adiposity-induced insulin-resistance (IR) and/or type 2 diabetes mellitus (T2D). We will briefly discuss the (patho)physiological functions of GLP-1 and GIP signaling in AT in this review, emphasizing their potential impacts on lipid storage, adipogenesis, glucose metabolism and inflammation. We will also address the conundrum with the perturbation of the incretin axis in white or brown fat tissue and the emergence of metabolic disorders. In order to reduce or avoid adiposity-related metabolic complications, we will finally go over a potential scientific rationale for suggesting AT as a novel target for GLP-1 and GIP receptor agonists and co-agonists. [ABSTRACT FROM AUTHOR]
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- 2024
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24. Myostatin regulates energy homeostasis through autocrine- and paracrine-mediated microenvironment communication.
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Hui Wang, Shanshan Guo, Huanqing Gao, Jiyang Ding, Hongyun Li, Xingyu Kong, Shuang Zhang, Muyang He, Yonghao Feng, Wei Wu, Kexin Xu, Yuxuan Chen, Hanyin Zhang, Tiemin Liu, and Xingxing Kong
- Subjects
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HOMEOSTASIS , *MYOSTATIN , *FIBROBLAST growth factors , *WEIGHT gain , *BROWN adipose tissue - Abstract
Myostatin (MSTN) has long been recognized as a critical regulator of muscle mass. Recently, there has been increasing interest in its role in metabolism. In our study, we specifically knocked out MSTN in brown adipose tissue (BAT) from mice (MSTNΔUCP1) and found that the mice gained more weight than did controls when fed a high-fat diet, with progressive hepatosteatosis and impaired skeletal muscle activity. RNA-Seq analysis indicated signatures of mitochondrial dysfunction and inflammation in the MSTN-ablated BAT. Further studies demonstrated that Kruppel-like factor 4 (KLF4) was responsible for the metabolic phenotypes observed, whereas fibroblast growth factor 21 (FGF21) contributed to the microenvironment communication between adipocytes and macrophages induced by the loss of MSTN. Moreover, the MSTN/SMAD2/3-p38 signaling pathway mediated the expression of KLF4 and FGF21 in adipocytes. In summary, our findings suggest that brown adipocyte--derived MSTN regulated BAT thermogenesis via autocrine and paracrine effects on adipocytes or macrophages, ultimately regulating systemic energy homeostasis. [ABSTRACT FROM AUTHOR]
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- 2024
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25. Sympathetic innervation of interscapular brown adipose tissue is not a predominant mediator of oxytocin-elicited reductions of body weight and adiposity in male diet-induced obese mice.
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Edwards, Melise M., Nguyen, Ha K., Dodson, Andrew D., Herbertson, Adam J., Wolden-Hanson, Tami, Wietecha, Tomasz A., Honeycutt, Mackenzie K., Slattery, Jared D., O'Brien, Kevin D., Graham, James L., Havel, Peter J., Mundinger, Thomas O., Sikkema, Carl L., Peskind, Elaine R., Ryu, Vitaly, Taborsky Jr., Gerald J., and Blevins, James E.
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WEIGHT loss ,BROWN adipose tissue ,ADIPOSE tissues ,WHITE adipose tissue ,SYMPATHETIC nervous system - Abstract
Previous studies indicate that CNS administration of oxytocin (OT) reduces body weight in high fat diet-induced obese (DIO) rodents by reducing food intake and increasing energy expenditure (EE). We recently demonstrated that hindbrain (fourth ventricular [4V]) administration of OT elicits weight loss and elevates interscapular brown adipose tissue temperature (T
IBAT , a surrogate measure of increased EE) in DIO mice. What remains unclear is whether OT-elicited weight loss requires increased sympathetic nervous system (SNS) outflow to IBAT. We hypothesized that OT-induced stimulation of SNS outflow to IBAT contributes to its ability to activate BAT and elicit weight loss in DIO mice. To test this hypothesis, we determined the effect of disrupting SNS activation of IBAT on the ability of 4V OT administration to increase TIBAT and elicit weight loss in DIO mice. We first determined whether bilateral surgical SNS denervation to IBAT was successful as noted by ≥ 60% reduction in IBAT norepinephrine (NE) content in DIO mice. NE content was selectively reduced in IBAT at 1-, 6- and 7-weeks post-denervation by 95.9 ± 2.0, 77.4 ± 12.7 and 93.6 ± 4.6% (P<0.05), respectively and was unchanged in inguinal white adipose tissue, pancreas or liver. We subsequently measured the effects of acute 4V OT (1, 5 µg ≈ 0.99, 4.96 nmol) on TIBAT in DIO mice following sham or bilateral surgical SNS denervation to IBAT. We found that the high dose of 4V OT (5 µg ≈ 4.96 nmol) elevated TIBAT similarly in sham mice as in denervated mice. We subsequently measured the effects of chronic 4V OT (16 nmol/day over 29 days) or vehicle infusions on body weight, adiposity and food intake in DIO mice following sham or bilateral surgical denervation of IBAT. Chronic 4V OT reduced body weight by 5.7 ± 2.23% and 6.6 ± 1.4% in sham and denervated mice (P<0.05), respectively, and this effect was similar between groups (P=NS). OT produced corresponding reductions in whole body fat mass (P<0.05). Together, these findings support the hypothesis that sympathetic innervation of IBAT is not necessary for OT-elicited increases in BAT thermogenesis and reductions of body weight and adiposity in male DIO mice. [ABSTRACT FROM AUTHOR]- Published
- 2024
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26. Attenuation of brown adipocyte whitening in high‐fat diet‐induced obese rats: Effects of melatonin and β‐hydroxybutyrate on Cidea, Fsp27 and MT1 expression.
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Maleki, Mohammad Hasan, Khakshournia, Sara, Heydarnia, Emad, Omidi, Fateme, Taghizadeh, Motahareh, Zeynolabedinzadeh, Mahroo, Akbari, Mohammadarian, Vakili, Omid, and Shafiee, Sayed Mohammad
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BROWN adipose tissue , *WHITE adipose tissue , *ORAL drug administration , *UNCOUPLING proteins , *GENE expression - Abstract
Aim Methods Results Conclusion To investigate the effects of β‐hydroxybutyrate (BHB) and melatonin on brown adipose tissue (BAT) plasticity in rats fed a high‐fat diet (HFD).We employed a 7‐week experimental design for a study on 30 male Sprague–Dawley rats divided into five groups: (1) a control‐diet fed group; (2) a high‐fat diet (HFD)‐fed group; (3) a group that received an HFD and a BHB solution in their drinking water; (4) a group that received an HFD with 10 mg/kg/day melatonin in their drinking water; and (5) a group that received an HFD and were also treated with the combination of BHB and melatonin. Following the treatment period, biochemical indices, gene expression levels of key thermogenic markers (including uncoupling protein 1 [UCP1], PR domain containing 16 [PRDM16], Cidea, fat‐specific protein 27 [Fsp27], and metallothionein 1 [MT1]), and stereological assessments of BAT were evaluated.Treatment with BHB and melatonin significantly boosted blood ketone levels, improved lipid profiles, and reduced weight gain from an HFD. It also downregulated genes linked to WAT, namely, Cidea and Fsp27, and upregulated key BAT markers, including UCP1, PRDM16 and peroxisome proliferator‐activated receptor‐gamma coactivator‐1‐alpha. Additionally, the co‐treatment increased MT1 receptor expression and enhanced the structural density of BAT.The combined oral administration of BHB and melatonin successfully prevented the whitening of BAT in obese rats fed an HFD, indicating its potential as a therapeutic strategy for obesity‐related BAT dysfunction. The synergistic effects of this treatment underscore the potential of a combined approach to address BAT dysfunction in obesity. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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27. Light-responsive adipose-hypothalamus axis controls metabolic regulation.
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Tsuji, Tadataka, Tolstikov, Vladimir, Zhang, Yang, Huang, Tian Lian, Camara, Henrique, Halpin, Meghan, Narain, Niven R., Yau, King-Wai, Lynes, Matthew D., Kiebish, Michael A., and Tseng, Yu-Hua
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BROWN adipose tissue ,WHITE adipose tissue ,CRYPTOCHROMES ,SYMPATHETIC nervous system ,BLUE light ,HYPOTHALAMUS - Abstract
Light is fundamental for biological life, with most mammals possessing light-sensing photoreceptors in various organs. Opsin3 is highly expressed in adipose tissue which has extensive communication with other organs, particularly with the brain through the sympathetic nervous system (SNS). Our study reveals a new light-triggered crosstalk between adipose tissue and the hypothalamus. Direct blue-light exposure to subcutaneous white fat improves high-fat diet-induced metabolic abnormalities in an Opsin3-dependent manner. Metabolomic analysis shows that blue light increases circulating levels of histidine, which activates histaminergic neurons in the hypothalamus and stimulates brown adipose tissue (BAT) via SNS. Blocking central actions of histidine and denervating peripheral BAT blunts the effects of blue light. Human white adipocytes respond to direct blue light stimulation in a cell-autonomous manner, highlighting the translational relevance of this pathway. Together, these data demonstrate a light-responsive metabolic circuit involving adipose-hypothalamus communication, offering a potential strategy to alleviate obesity-induced metabolic abnormalities. Light is essential for biological life. Here, the authors show blue light activates the photoreceptor Opsin3 in white fat, triggering a light-responsive metabolic circuit involving adipose-hypothalamus communication, which could potentially alleviate obesity-induced metabolic abnormalities. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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28. Brown adipose tissue-derived FGF21 mediates the cardioprotection of dexmedetomidine in myocardial ischemia/reperfusion injury.
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Ding, Yi, Su, Jiabao, Shan, Beiying, Fu, Xiao, Zheng, Guanli, Wang, Jiwen, Wu, Lixue, Wang, Fangming, Chai, Xiaoying, Sun, Haijian, and Zhang, Jiru
- Abstract
Brown adipose tissue (BAT) plays a critical role in regulating cardiovascular homeostasis through the secretion of adipokines, such as fibroblast growth factor 21 (FGF21). Dexmedetomidine (DEX) is a selective α2-adrenergic receptor agonist with a protection against myocardial ischemia/reperfusion injury (MI/RI). It remains largely unknown whether or not BAT-derived FGF21 is involved in DEX-induced cardioprotection in the context of MI/RI. Herein, we demonstrated that DEX alleviated MI/RI and improved heart function through promoting the release of FGF21 from interscapular BAT (iBAT). Surgical iBAT depletion or supplementation with a FGF21 neutralizing antibody attenuated the beneficial effects of DEX. AMPK/PGC1α signaling-induced fibroblast growth factor 21 (FGF21) release in brown adipocytes is required for DEX-mediated cardioprotection since blockade of the AMPK/PGC1α axis weakened the salutary effects of DEX. Co-culture experiments showed that DEX-induced FGF21 from brown adipocytes increased the resistance of cardiomyocytes to hypoxia/reoxygenation (H/R) injury via modulating the Keap1/Nrf2 pathway. Our results provided robust evidence that the BAT-cardiomyocyte interaction is required for DEX cardioprotection, and revealed an endocrine role of BAT in DEX-mediating protection of hearts against MIRI. [ABSTRACT FROM AUTHOR]
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- 2024
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29. Is irisin really a neuroendocrine (f)actor?
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Sandal, Suleyman, Unuvar, Songul, and Yilmaz, Bayram
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IRISIN , *PEPTIDE hormones , *FOOD consumption , *OBESITY , *BROWN adipose tissue , *CARDIOVASCULAR system - Abstract
Irisin was identified as a peptide hormone in 2012. The most important known physiological effect of irisin is that it activates uncoupling protein 1 and converts white adipose tissue to brown adipose tissue. Due to this effect of irisin on adipose tissue, it was thought that it may be closely related to obesity, feeding behavior and energy expenditure, and interest in research in this direction has increased. Later studies revealed that irisin, beyond its known effects, also influences the reproductive, nervous, cardiovascular, and excretory systems. Recent studies have determined that irisin has anti-oxidant, anti-inflammatory and anti-apoptotic properties, and it has been reported that pathologies such as obesity, endocrine and metabolic diseases, Alzheimer's disease, chronic kidney disease, cardiovascular diseases, atherosclerosis and cancer may be associated with changes irisin levels. The fact that irisin is expressed in different tissues other than muscle and fat tissue and exhibits autocrine and endocrine functions, as well as being expressed in different regions of the brain and participating in neuroendocrine processes in these regions, brings to mind that irisin may be a new neuroendocrine factor. In this review, we present information that will constitute evidence that irisin is a real neuroendocrine factor. [ABSTRACT FROM AUTHOR]
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- 2024
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30. TLCD4 as Potential Transcriptomic Biomarker of Cold Exposure.
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Reynés, Bàrbara, García-Ruiz, Estefanía, van Schothorst, Evert M., Keijer, Jaap, Oliver, Paula, and Palou, Andreu
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MONONUCLEAR leukocytes , *GENE expression , *BROWN adipose tissue , *ADIPOSE tissues , *BIOMARKERS , *RATS - Abstract
(1) Background: Cold exposure induces metabolic adaptations that can promote health benefits, including increased energy disposal due to lipid mobilization in adipose tissue (AT). This study aims to identify easily measurable biomarkers mirroring the effect of cold exposure on AT. (2) Methods: Transcriptomic analysis was performed in peripheral blood mononuclear cells (PBMCs) and distinct AT depots of two animal models (ferrets and rats) exposed to cold, and in PBMCs of cold-exposed humans. (3) Results: One week of cold exposure (at 4 °C) affected different metabolic pathways and gene expression in the AT of ferrets, an animal model with an AT more similar to humans than that of rodents. However, only one gene, Tlcd4, was affected in the same way (overexpressed) in aortic perivascular and inguinal AT depots and in PBMCs, making it a potential biomarker of interest. Subsequent targeted analysis in rats showed that 1 week at 4 °C also induced Tlcd4 expression in brown AT and PBMCs, while 1 h at 4 °C resulted in reduced Tlcd4 mRNA levels in retroperitoneal white AT. In humans, no clear effects were observed. Nevertheless, decreased PBMC TLCD4 expression was observed after acute cold exposure in women with normal weight, although this effect could be attributed to short-term fasting during the procedure. No effect was evident in women with overweight or in normal-weight men. (4) Conclusions: Our results obtained for different species point toward TLCD4 gene expression as a potential biomarker of cold exposure/fat mobilization that could tentatively be used to address the effectiveness of cold exposure-mimicking therapies. [ABSTRACT FROM AUTHOR]
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- 2024
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31. Heterogeneous metabolic changes of brown and white adipose tissues are associated with metabolic adaptations in periparturient mice.
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Gang Wei, Juan-Juan Zhu, Feng-Jie Shen, Rong-Rong Xie, Chen-Yang Zhang, Yuan Wang, Ting-Ting Shi, Xi Cao, Xin Ding, and Jin-Kui Yang
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WHITE adipose tissue , *BROWN adipose tissue , *INSULIN resistance , *GLUCOSE intolerance , *PREGNANT women , *ADIPOSE tissues , *MAMMARY glands - Abstract
Pregnancy requires metabolic adaptations in order to meet support fetal growth with nutrient availability. In this study, the influence of pregnancy on metabolically active organs (adipose tissues in particular) was investigated. Our results showed that maternal weight and adipose mass presented dynamic remodeling in the periparturient mice. Meanwhile, pregnancy mice displayed obvious glucose intolerance and insulin resistance in late pregnancy as compared to non-pregnancy, which were partially reversed at parturition. Further analyses revealed that different fat depots exhibited site-specific adaptions of morphology and functionality as pregnancy advanced. Brown and inguinal white adipose tissue (BAT and IngWAT) exhibited obviously decreased thermogenic activity; by contrast, gonadal white adipose tissue (GonWAT) displayed remarkably increased lipid mobilization. Notably, we found that mammary gland differentiation was enhanced in IngWAT, followed by BAT but not in GonWAT. These result indicated that brown and white adipose tissues might synergistically play a crucial role in maintaining the maximum of energy supply for mother and fetus, which facilitates the mammary duct luminal epithelium development as well as the growth and development of fetus. Accompanied with adipose adaptation, however, our results revealed that the liver and pancreas also displayed significant metabolic adaptability, which together tended to trigger the risk of maternal metabolic diseases. Importantly, pregnancy-dependent obesity in our mice model resembled the disturbed metabolic phenotypes of pregnant women such as hyperglyceridemia and hypercholesterolemia. Our findings in this study could provide valuable clues for better understanding the underlying mechanisms of metabolic maladaptation and facilitate the development of the prevention and treatment of metabolic diseases. [ABSTRACT FROM AUTHOR]
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- 2024
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32. Obesity‐induced tissue alterations resist weight loss: A mechanistic review.
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Della Guardia, Lucio and Shin, Andrew C.
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WEIGHT loss , *LIPOLYSIS , *SKELETAL muscle , *BROWN adipose tissue , *FAT cells , *FAT , *SARCOPLASMIC reticulum , *NUTRITIONAL status - Abstract
Interventions aimed at weight control often have limited effectiveness in combating obesity. This review explores how obesity‐induced dysfunction in white (WAT) and brown adipose tissue (BAT), skeletal muscle, and the brain blunt weight loss, leading to retention of stored fat. In obesity, increased adrenergic stimulation and inflammation downregulate β‐adrenoreceptors and impair catecholaminergic signalling in adipocytes. This disrupts adrenergic‐mediated lipolysis, diminishing lipid oxidation in both white and brown adipocytes, lowering thermogenesis and blunting fat loss. Emerging evidence suggests that WAT fibrosis is associated with worse weight loss outcomes; indeed, limiting collagen and laminin‐α4 deposition mitigates WAT accumulation, enhances browning, and protects against high‐fat‐diet‐induced obesity. Obesity compromises mitochondrial oxidative capacity and lipid oxidation in skeletal muscle, impairing its ability to switch between glucose and lipid metabolism in response to varying nutrient levels and exercise. This dysfunctional phenotype in muscle is exacerbated in the presence of obesity‐associated sarcopenia. Additionally, obesity suppresses sarcolipin‐induced sarcoplasmic reticulum calcium ATPase (SERCA) activation, resulting in reduced oxidative capacity, diminished energy expenditure, and increased adiposity. In the hypothalamus, obesity and overnutrition impair insulin and leptin signalling. This blunts central satiety signals, favouring a shift in energy balance toward energy conservation and body fat retention. Moreover, both obese animals and humans demonstrate impaired dopaminergic signalling and diminished responses to nutrient intake in the striatum, which tend to persist after weight loss. This may result in enduring inclinations toward overeating and a sedentary lifestyle. Collectively, the tissue adaptations described pose significant challenges to effectively achieving and sustaining weight loss in obesity. [ABSTRACT FROM AUTHOR]
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- 2024
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33. Human adipose tissue expression of uncoupling protein 1 in response to intravenous administration of B‐type natriuretic peptide hormone: Results from a randomized controlled crossover study.
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Bachmann, Katherine N., Ceddia, Ryan P., Gupta, Deepak K., Collins, Sheila, and Wang, Thomas J.
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ADIPOSE tissues , *PEPTIDE hormones , *UNCOUPLING proteins , *LIPOLYSIS , *INTRAVENOUS therapy , *ABDOMINAL adipose tissue , *BROWN adipose tissue - Abstract
A recent study published in the journal Diabetes, Obesity & Metabolism investigated the effects of B-type natriuretic peptide (BNP) hormone on adipose tissue in humans. The study found that a 4-hour infusion of BNP led to a two- to five-fold increase in the expression of uncoupling protein 1 (UCP1), a marker of brown/beige adipocytes. This suggests that BNP may promote adipocyte thermogenesis and beiging, which could have implications for the treatment of obesity. The study had a small sample size and did not include women, so further research is needed to confirm these findings. [Extracted from the article]
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- 2024
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34. TRPV1 Activation Antagonizes High-Fat Diet-Induced Obesity at Thermoneutrality and Enhances UCP-1 Transcription via PRDM-16.
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Baskaran, Padmamalini, Gustafson, Noah, and Chavez, Nicolas
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BROWN adipose tissue , *MITOCHONDRIAL proteins , *WEIGHT gain , *UNCOUPLING proteins , *GENETIC transcription - Abstract
Body weight is a balance between energy intake and energy expenditure. Energy expenditure is mainly governed by physical activity and adaptive thermogenesis. Adaptive dietary thermogenesis in brown and beige adipose tissue occurs through mitochondrial uncoupling protein (UCP-1). Laboratory mice, when housed at an ambient temperature of 22–24 °C, maintain their body temperature by dietary thermogenesis, eating more food compared to thermoneutrality. Humans remain in the thermoneutral zone (TNZ) without expending extra energy to maintain normal body temperature. TRPV1 activation by capsaicin (CAP) inhibited weight gain in mice housed at ambient temperature by activating UCP-1-dependent adaptive thermogenesis. Hence, we evaluated the effect of CAP feeding on WT and UCP-1−/− mice maintained under thermoneutral conditions. Our research presents novel findings that TRPV1 activation by CAP at thermoneutrality counters obesity in WT mice and promotes PRDM-16-dependent UCP-1 transcription. CAP fails to inhibit weight gain in UCP-1−/− mice housed at thermoneutrality and in adipose tissue-specific PRDM-16−/− mice. In vitro, capsaicin treatment increases UCP-1 transcription in PRDM-16 overexpressing cells. Our data indicate for the first time that TRPV1 activation counters obesity at thermoneutrality permissive for UCP-1 and the enhancement of PRDM-16 is not beneficial in the absence of UCP-1. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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35. Glucocorticoid modulates oxidative and thermogenic function of rat brown adipose tissue and human brown adipocytes.
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Bolin, Anaysa Paola, Fatima Silva, Flaviane, Salgueiro, Rafael Barrera, Santos, Bruna Araújo, Komino, Ayumi Cristina Medeiros, Andreotti, Sandra, Sousa, Érica, Castro, Érique, Real, Caroline Cristiano, Paula Faria, Daniele, Souza, Gerson Profeta, Camara, Henrique, Sorgi, Carlos Arterio, Tseng, Yu‐Hua, Lima, Fábio Bessa, and Rodrigues, Alice Cristina
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BROWN adipose tissue , *HUMAN biology , *CUSHING'S syndrome , *FAT cells , *RATTUS norvegicus - Abstract
Chronic and excessive glucocorticoid (GC) exposure can cause Cushing's syndrome, resulting in fat accumulation in selected body areas. Particularly in the brown adipose tissue (BAT), GC acts negatively, resulting in whitening of the tissue. We hypothesized that dysregulation of microRNAs by GC could be an additional mechanism to explain its negative actions in BAT. Male Wistar rats were divided into two groups: (1) Control sham and (2) GC group that was administered dexamethasone 6.25 mg/200 μL via osmotic pump implantation over 28 days. After this period, the animals were euthanized and BAT tissue was properly stored. Human fat cells treated with dexamethasone were used to translate the experimental results found in animals to human biology. GC‐treated rat BAT presented with large lipid droplets, severely impaired thermogenic activation, and reduced glucose uptake measured by 18F‐FDG PET/CT. GC exposure induced a reduction in the mitochondrial OXPHOS system and oxygen consumption. MicroRNA profiling of BAT revealed five top‐regulated microRNAs and among them miR‐21‐5p was the most significantly upregulated in GC‐treated rats compared to the control group. Although upregulation of miR‐21‐5p in the tissue, differentiated primary brown adipocytes from GC‐treated rats had decreased miR‐21‐5p levels compared to the control group. To translate these results to the clinic, human brown adipocytes were treated with dexamethasone and miR‐21‐5p inhibitor. In human brown cells, inhibition of miR‐21‐5p increased brown adipocyte differentiation and prevented GC‐induced glucose uptake, resulting in a lower glycolysis rate. In conclusion, high‐dose GC therapy significantly impacts brown adipose tissue function, with a notable association between glucose uptake and miR‐21‐5p. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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36. Thermoneutrality Inhibits Thermogenic Markers and Exacerbates Nonalcoholic Fatty Liver Disease in Mice.
- Author
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Hao, Lei, Khan, Md Shahjalal Hossain, Zu, Yujiao, Liu, Jie, and Wang, Shu
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STEROL regulatory element-binding proteins , *NON-alcoholic fatty liver disease , *FATTY acid synthases , *BROWN adipose tissue , *WHITE adipose tissue - Abstract
Nonalcoholic fatty liver disease (NAFLD) affects over a third of the US population and 25% globally, with current treatments proving ineffective. This study investigates whether manipulating brown adipose tissue (BAT) and beige fat activity by housing C57BL/6J mice at thermoneutral (27 °C) or standard temperatures (22 °C) impacts NAFLD development. Male mice were fed either a chow diet (CHD) or a "fast food" diet (FFD) for 10 weeks. Mice at 27 °C had reduced food intake but increased body weight and plasma leptin levels. FFD-fed mice at 27 °C had greater liver weight (2.6 vs. 1.8 g), triglyceride content (7.6 vs. 3.9 mg/g), and hepatic steatosis compared to those at 22 °C. Gene expression of fatty acid synthase, sterol regulatory element-binding protein 1, and fatty acid translocase CD36 was elevated in FFD-fed mice at 27 °C, but not in CHD-fed mice. Thermoneutral housing also reduced expression of thermogenic markers in BAT and inguinal white adipose tissue (WAT) and caused BAT whitening. In conclusion, thermoneutrality inhibits thermogenic markers and exacerbates NAFLD. Activating BAT or promoting WAT browning via cold exposure or other stimuli may offer a strategy for managing NAFLD. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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37. A device for rapid calorimetric measurements on small biological tissue samples.
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Lerchner, Johannes, Hervas, Livia S., Bícego, Kenia C., Garcia, Geovana S., Oliveira, Marcos T., Hasic, Mersiha, Klingenspor, Martin, and Mertens, Florian
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BROWN adipose tissue , *TISSUES , *BIOMATERIALS , *DROSOPHILA , *LIZARDS - Abstract
A new calorimetric technique is described that allows high-throughput heat production rate measurements on small biological tissue samples. The technique is based on the widely used thermopile chip technology combined with an innovative method for precise transport and positioning of samples of different biological materials at the thermal power detector inside the calorimeter. The new transport and positioning technique is a combination of fluidic and mechanical transport, where the latter is realized by a magneto-motor drive. The transport facility ensures good diffusive oxygen penetration into the sample, which is essential for highly metabolically active materials. The proper functioning of the device is demonstrated by measuring the heat production of metabolically active brown adipose tissue, biopsied tegu lizard muscle, and live Drosophila larvae at different stages and temperatures. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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38. Mice Lacking Mrs2 Magnesium Transporter are Hypophagic and Thin When Maintained on a High-Fat Diet.
- Author
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Powell, David R, Doree, Deon D, Shadoan, Melanie K, Platt, Kenneth A, Brommage, Robert, Vogel, Peter, and Revelli, Jean-Pierre
- Subjects
HIGH-fat diet ,BROWN adipose tissue ,WHITE adipose tissue ,HOMOLOGOUS recombination ,INSULIN sensitivity - Abstract
Genes regulating body fat are shared with high fidelity by mice and humans, indicating that mouse knockout (KO) phenotyping might identify valuable antiobesity drug targets. Male Mrs2 magnesium transporter (Mrs2) KO mice were recently reported as thin when fed a high-fat diet (HFD). They also exhibited increased energy expenditure (EE)/body weight and had beiged adipocytes that, along with isolated hepatocytes, demonstrated increased oxygen consumption, suggesting that increased EE drove the thin phenotype. Here we provide our data on these and additional assays in Mrs2 KO mice. We generated Mrs2 KO mice by homologous recombination. HFD-fed male and female Mrs2 KO mice had significantly less body fat, measured by quantitative magnetic resonance, than wild-type (WT) littermates. HFD-fed Mrs2 KO mice did not demonstrate increased EE by indirect calorimetry and could not maintain body temperature at 4 °C, consistent with their decreased brown adipose tissue stores but despite increased beige white adipose tissue. Instead, when provided a choice between HFD and low-fat diet (LFD), Mrs2 KO mice showed a significant 15% decrease in total energy intake resulting from significantly lower HFD intake that offset numerically increased LFD intake. Food restriction studies performed using WT mice suggested that this decrease in energy intake could explain the loss of body fat. Oral glucose tolerance test studies revealed significantly improved insulin sensitivity in Mrs2 KO mice. We conclude that HFD-fed Mrs2 KO mice are thin with improved insulin sensitivity, and that this favorable metabolic phenotype is driven by hypophagia. Further evaluation is warranted to determine the suitability of MRS2 as a drug target for antiobesity therapeutics. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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39. White adipocyte-derived exosomal miR-23b inhibits thermogenesis by targeting Elf4 to regulate GLP-1R transcription.
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Wang, Qian, Du, Junkai, and Ma, Ruili
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BROWN adipose tissue ,WHITE adipose tissue ,GENE expression ,PROMOTERS (Genetics) ,BODY weight - Abstract
Promoting non-trembling thermogenesis of brown adipose tissue (BAT) and browning of white adipose tissue (WAT) helps prevent obesity. MiR-23b is highly expressed in adipose tissue-derived exosomes obtained from obese people, but the role of exosomal miR-23b in regulating thermogenesis and obesity progression remains to be further explored. Here, a mouse obesity model was established through high-fat diet (HFD), and inguinal WAT (iWAT)-derived exosomes and miR-23b antagomir were administered by intraperitoneal injection. The results showed that WAT-derived exosomal miR-23b upregulated body weight and adipocyte hypertrophy and enhanced insulin resistance. Moreover, exosomal miR-23b restrained mtDNA copy number and the expression of genes related to thermogenesis and mitochondrial biogenesis in BAT, and suppressed the expression of WAT browning-related genes under cold stimulation, indicating that exosomal miR-23b hindered non-trembling thermogenesis of BAT and WAT browning. Mechanism studies found that miR-23b targeted Elf4 to inhibit its expression. And Elf4 bound to the GLP-1R promoter region to promote GLP-1R transcription. In addition, silencing miR-23b effectively abolished the inhibitory effect of WAT-derived exosomes on thermogenic gene expression and mitochondrial respiration in adipocytes isolated from BAT and iWAT, which was reversed by GLP-1R knockdown. In conclusion, WAT-derived exosomal miR-23b suppressed thermogenesis by targeting Elf4 to regulate GLP-1R transcription, which contributed to the progression of obesity. [ABSTRACT FROM AUTHOR]
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- 2024
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40. Brown fat-specific mitoribosomal function is crucial for preventing cold exposure-induced bone loss.
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Tian, Jingwen, Moon, Ji Sun, Nga, Ha Thi, Lee, Ho Yeop, Nguyen, Thi Linh, Jang, Hyo Ju, Setoyama, Daiki, Shong, Minho, Lee, Ju Hee, and Yi, Hyon-Seung
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BONE density , *PHYSIOLOGICAL effects of cold temperatures , *BONE health , *BROWN adipose tissue , *BONE metabolism , *BONE remodeling , *BONE marrow - Abstract
This study examines the interplay between ambient temperature, brown adipose tissue (BAT) function, and bone metabolism, emphasizing the effects of cold exposure and BAT mitochondrial activity on bone health. Utilizing ovariectomized (OVX) mice to model primary osteoporosis and BAT-specific mitochondrial dysfunction (BKO) mice, we evaluated the impact of housing temperature on bone density, immune modulation in bone marrow, and the protective role of BAT against bone loss. Cold exposure was found to universally reduce bone mass, enhance osteoclastogenesis, and alter bone marrow T-cell populations, implicating the immune system in bone remodeling under cold stress. The thermogenic function of BAT, driven by mitochondrial oxidative phosphorylation, was crucial in protecting against bone loss. Impaired BAT function, through surgical removal or mitochondrial dysfunction, exacerbated bone loss in cold environments, highlighting BAT's metabolic role in maintaining bone health. Furthermore, cold-induced changes in BAT function led to systemic metabolic shifts, including elevated long-chain fatty acids, which influenced osteoclast differentiation and activity. These findings suggest a systemic mechanism connecting environmental temperature and BAT metabolism with bone physiology, providing new insights into the metabolic and environmental determinants of bone health. Future research could lead to novel bone disease therapies targeting these pathways. [ABSTRACT FROM AUTHOR]
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- 2024
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41. Topical menthol, a pharmacological cold mimic, induces cold sensitivity, adaptive thermogenesis and brown adipose tissue activation in mice.
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Sankina, Polina, Lal, Roshan, Khare, Pragyanshu, Hörsten, Stephan, Fester, Lars, Aggarwal, Vaishali, Zimmermann, Katharina, and Bishnoi, Mahendra
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BROWN adipose tissue , *MENTHOL , *BODY temperature regulation , *INSULIN , *TOPICAL drug administration , *TYROSINE hydroxylase , *WEIGHT gain - Abstract
Aim Methods Results Brown adipose tissue (BAT) thermogenesis has profound energy‐expanding potential, which makes it an attractive target tissue to combat ever‐increasing obesity and its other associated metabolic complications. Although it is fairly accepted that cold is a potent inducer of BAT activation and function, there are limited studies on the mechanisms of pharmacological cold‐mimicking agents, such as the TRPM8 agonist, menthol, on BAT thermogenesis and activation.Herein, we sought to determine the effect of topical application of menthol (10% w/v [4 g/kg] cream formulation/day for 15 days) on temperature sensitivity behaviour (thermal gradient assay, nesting behaviour), adaptive thermogenesis (infrared thermography, core body temperature), BAT sympathetic innervation (tyrosine hydroxylase immunohistochemistry) and activation (18F‐FDG PET‐CT analysis, Uncoupling Protein 1 immunohistochemistry and BAT gene expression), whole‐body energy expenditure (indirect calorimetry) and other metabolic variables in male C57BL/6N mice.We show that male C57BL/6N mice: (a) develop a warm‐seeking and cold‐avoiding thermal preference phenotype; (b) display increased locomotor activity and adaptive thermogenesis; (c) show augmented sympathetic innervation in BAT and its activation; (d) exhibit enhanced gluconeogenic capacity (increased glucose excursion in response to pyruvate) and insulin sensitivity; and (e) show enhanced whole‐body energy expenditure and induced lipid‐utilizing phenotype after topical menthol application. Conclusions: Taken together, our findings highlight that pharmacological cold mimicking using topical menthol application presents a potential therapeutic strategy to counter weight gain and related complications. [ABSTRACT FROM AUTHOR]
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- 2024
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42. Role of Brown Adipose Tissue in Metabolic Health and Efficacy of Drug Treatment for Obesity.
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Markina, Natalia O., Matveev, Georgy A., Zasypkin, German G., Golikova, Tatiana I., Ryzhkova, Daria V., Kononova, Yulia A., Danilov, Sergey D., and Babenko, Alina Yu.
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POSITRON emission tomography computed tomography , *BROWN adipose tissue , *DUAL-energy X-ray absorptiometry , *POSITRON emission tomography , *WEIGHT loss - Abstract
(1) Background: Brown adipose tissue (BAT) is responsible for non-shivering thermogenesis, and its activation has become a new object as both a determinant of metabolic health and a target for therapy. This study aimed to identify the relationships between the presence of BAT, parameters that characterize metabolic health (glucose, lipids, blood pressure (BP)), and the dynamics of body mass index (BMI) during weight-reducing therapy. (2) Methods: The study included 72 patients with obesity. We investigated metabolic parameters, anthropometric parameters, and BP. Dual-energy X-ray absorptiometry (DXA) and positron emission tomography and computed tomography (PET/CT) imaging with 18F-fluorodeoxyglucose (18F-FDG) were performed. (3) Results: Before weight-reducing therapy, BAT was revealed only in 19% patients with obesity. The presence of BAT was associated with a lower risk of metabolic deviations that characterize metabolic syndrome: shorter waist circumference (WC) (p = 0.02) and lower levels of glucose (p = 0.03) and triglycerides (p = 0.03). Thereafter, patients were divided into four groups according to the type of therapy (only lifestyle modification or with Liraglutide or Reduxin or Reduxin Forte). We did not find a relationship between the presence of BAT and response to therapy: percent weight reduction was 10.4% in patients with BAT and 8.5% in patients without BAT (p = 0.78) during six months of therapy. But we noted a significant positive correlation between the volume of BAT and the effectiveness of weight loss at 3 months (r = 0.52, p = 0.016). The dynamic analysis of BAT after 6 months of therapy showed a significant increase in the volume of cold-induced metabolically active BAT, as determined by PET/CT with 18F-FDG in the Liraglutide group (p = 0.04) and an increase in the activity of BAT standardized uptake value (SUV mean and SUV max) in the Reduxin (p = 0.02; p = 0.01, respectively) and Liraglutide groups (p = 0.02 in both settings). (4) Conclusions: The presence of brown adipose tissue is associated with a lower risk of metabolic abnormalities. In general, our study demonstrated that well-established drugs in the treatment of obesity (Liraglutide and Reduxin) have one more mechanism for implementing their effects. These drugs have the ability to increase the activity of BAT. A significant positive relationship between the total volume of BAT and the percentage of weight loss may further determine the priority mechanism of the weight-reducing effect of these medicaments. [ABSTRACT FROM AUTHOR]
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- 2024
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43. The therapeutic effect of NRF2 activator, ezetimibe, in cardiac cachexia.
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Vashi, Ruju, Joshi, Mit, and Patel, Bhoomika M.
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HEART , *CACHEXIA , *ADIPOSE tissues , *BROWN adipose tissue , *DRINKING (Physiology) , *EZETIMIBE , *NUCLEAR factor E2 related factor - Abstract
Introduction Method Result Conclusion Heart failure (HF) is caused by functional and structural irregularity leading to impaired ejection or filling capacity of the heart. HF leads to chronic inflammatory conditions in the heart leads to weight loss, anorexia, and muscle atrophy known as cachexia. The present study was carried out to investigate the role of Ezetimibe, an NRF2 activator, in cardiac cachexia and to develop a treatment strategy for cardiac cachexia.Balb/c mice of either sex at 6–8 weeks of age were given 2 mg/kg of doxorubicin in 0.9% sodium chloride solution intraperitoneally (i.p.) for the alternate days for the first week and then once a week for the next 4 weeks. After induction of cardiac atrophy, treatment with Ezetimibe (1.5 mg/kg,
p.o ) was given for the next 4 weeks.In the cardiac cachectic animals, a significant decrease in body weight, food, and water intake was observed. Cardiac cachectic animals showed a significant increase in serum glucose, total cholesterol, LDL, triglyceride, VLDL, CK‐MB, LDH, and CRP levels. Cardiac atrophic index, heart weight to body weight ratios (HW/BW), right ventricular weight to heart weight ratios (RV/HW), and left ventricular weight to heart weight ratios (LV/HW), were significantly decreased in cardiac cachectic animals. The weights of the skeletal muscles such as EDL, gastrocnemius, soleus, tibialis anterior, and quadriceps muscles, and the weight of adipose tissue such as subcutaneous, visceral, perirenal, and brown adipose tissue were significantly decreased in the cardiac cachectic group relative to the normal group. Treatment with ezetimibe improves body weight, food intake, and water intake. Ezetimibe decreases serum glucose, total cholesterol, LDL, triglyceride, VLDL, CK‐MB, LDH and CRP levels. Cardiac atrophic markers such as HW/BW, RV/HW, and LV/HW were improved. The weight of skeletal muscles and adipose tissue was increased after treatment with ezetimibe.Our data showed that the NRF2 activator, Ezetimibe produces a beneficial effect on cardiac cachexia in the doxorubicin‐induced cardiac cachexia model. Ezetimibe was successful to reduce the levels of inflammatory cytokines, ameliorate the effects on cardiac muscle wasting, lipid levels, fat tissues, and skeletal muscles. [ABSTRACT FROM AUTHOR]- Published
- 2024
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44. Adipose Tissue Dysfunction Related to Climate Change and Air Pollution: Understanding the Metabolic Consequences.
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Stojchevski, Radoslav, Chandrasekaran, Preethi, Hadzi-Petrushev, Nikola, Mladenov, Mitko, and Avtanski, Dimiter
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BROWN adipose tissue , *CLIMATE change , *AIR pollution , *DIETARY patterns , *TYPE 2 diabetes , *ADIPOSE tissues - Abstract
Obesity, a global pandemic, poses a major threat to healthcare systems worldwide. Adipose tissue, the energy-storing organ during excessive energy intake, functions as a thermoregulator, interacting with other tissues to regulate systemic metabolism. Specifically, brown adipose tissue (BAT) is positively associated with an increased resistance to obesity, due to its thermogenic function in the presence of uncoupled protein 1 (UCP1). Recently, studies on climate change and the influence of environmental pollutants on energy homeostasis and obesity have drawn increasing attention. The reciprocal relationship between increasing adiposity and increasing temperatures results in reduced adaptive thermogenesis, decreased physical activity, and increased carbon footprint production. In addition, the impact of climate change makes obese individuals more prone to developing type 2 diabetes mellitus (T2DM). An impaired response to heat stress, compromised vasodilation, and sweating increase the risk of diabetes-related comorbidities. This comprehensive review provides information about the effects of climate change on obesity and adipose tissue, the risk of T2DM development, and insights into the environmental pollutants causing adipose tissue dysfunction and obesity. The effects of altered dietary patterns on adiposity and adaptation strategies to mitigate the detrimental effects of climate change are also discussed. [ABSTRACT FROM AUTHOR]
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- 2024
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45. Dietary Pectin from Premna microphylla Turcz Leaves Prevents Obesity by Regulating Gut Microbiota and Lipid Metabolism in Mice Fed High-Fat Diet.
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Gao, Jiaobei, Zhang, Mengxue, Zhang, Li, Wang, Nan, Zhao, Yan, Ren, Daoyuan, and Yang, Xingbin
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LIPID metabolism disorders ,BROWN adipose tissue ,INSULIN sensitivity ,WEIGHT gain ,GALACTURONIC acid ,PECTINS - Abstract
The present study was designed to investigate the protective effects of pectin extracted from Premna microphylla Turcz leaves (PTP) against high-fat-diet (HFD)-induced lipid metabolism disorders and gut microbiota dysbiosis in obese mice. PTP was made using the acid extraction method, and it was found to be an acidic pectin that had relative mole percentages of 32.1%, 29.2%, and 26.2% for galacturonic acid, arabinose, and galactose, respectively. The administration of PTP in C57BL/6J mice inhibited the HFD-induced abnormal weight gain, visceral obesity, and dyslipidemia, and also improved insulin sensitivity, as revealed by the improved insulin tolerance and the decreased glucose levels during an insulin sensitivity test. These effects were linked to increased energy expenditure, as demonstrated by the upregulation of thermogenesis-related protein UCP1 expression in the brown adipose tissue (BAT) of PTP-treated mice. 16S rRNA gene sequencing revealed that PTP dramatically improved the HFD-induced gut dysbiosis by lowering the ratio of Firmicutes to Bacteroidetes and the quantity of potentially harmful bacteria. These findings may provide a theoretical basis for us to understand the functions and usages of PTP in alleviating obesity. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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46. MicroRNA-21 modulates brown adipose tissue adipogenesis and thermogenesis in a mouse model of polycystic ovary syndrome.
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Rezq, Samar, Huffman, Alexandra M., Basnet, Jelina, Alsemeh, Amira E., do Carmo, Jussara M., Yanes Cardozo, Licy L., and Romero, Damian G.
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POLYCYSTIC ovary syndrome , *INDUCED ovulation , *BROWN adipose tissue , *WEIGHT gain , *MICRORNA , *LEAN body mass , *BODY composition , *ADIPOSE tissues - Abstract
Background: Polycystic ovary syndrome (PCOS), the most common endocrine disorder in premenopausal women, is associated with increased obesity, hyperandrogenism, and altered brown adipose tissue (BAT) thermogenesis. MicroRNAs play critical functions in brown adipocyte differentiation and maintenance. We aim to study the role of microRNA-21 (miR-21) in altered energy homeostasis and BAT thermogenesis in a PCOS mouse model of peripubertal androgen exposure. Methods: Three-week-old miR-21 knockout (miR21KO) or wild-type (WT) female mice were treated with dihydrotestosterone (DHT) or vehicle for 90 days. Body composition was determined by EchoMRI. Energy expenditure (EE), oxygen consumption (VO2), carbon dioxide production (VCO2), and respiratory exchange ratio (RER) were measured by indirect calorimetry. Androgen receptor (AR), and markers of adipogenesis, de novo lipogenesis, angiogenesis, extracellular matrix remodeling, and thermogenesis were quantified by RT-qPCR and/or Western-blot. Results: MiR-21 ablation attenuated DHT-mediated increase in body weight while having no effect on fat or BAT mass. MiR-21 ablation attenuated DHT-mediated BAT AR upregulation. MiR-21 ablation did not alter EE; however, miR21KO DHT-treated mice have reduced VO2, VCO2, and RER. MiR-21 ablation reversed DHT-mediated decrease in food intake and increase in sleep time. MiR-21 ablation decreased some adipogenesis (Adipoq, Pparγ, and Cebpβ) and extracellular matrix remodeling (Mmp-9 and Timp-1) markers expression in DHT-treated mice. MiR-21 ablation abolished DHT-mediated increases in thermogenesis markers Cpt1a and Cpt1b, while decreasing CIDE-A expression. Conclusions: Our findings suggest that BAT miR-21 may play a role in regulating DHT-mediated thermogenic dysfunction in PCOS. Modulation of BAT miR-21 levels could be a novel therapeutic approach for the treatment of PCOS-associated metabolic derangements. Highlights: MicroRNA-21 genetic ablation decreased excess androgen-mediated increase in body weight and lean mass. Excess androgens decreased oxygen consumption (VO2), carbon dioxide production (VCO2), and respiratory exchange ratio (RER), without affecting energy expenditure (EE) in microRNA-21 knockout mice. MicroRNA-21 genetic ablation decreased the expression of some brown adipose tissue markers of adipogenesis in excess androgen-treated mice. MicroRNA-21 genetic ablation decreased the expression of some brown adipose tissue markers of extracellular matrix remodeling in excess androgen-treated mice. MicroRNA-21 genetic ablation reversed the androgen-mediated increased expression of some genes related to thermogenesis in brown adipose tissue of androgen-treated mice. Plain language summary: Polycystic ovary syndrome (PCOS) is a common hormone disorder in premenopausal women, often linked to obesity and abnormal brown fat tissue activity. Women with PCOS have elevated male hormones, which are responsible for many metabolic problems. Our study focuses on understanding the role of microRNA-21 (miR-21) in the energy balance and brown fat tissue activity in a PCOS mouse model. We studied female mice with and without miR-21, treating them with a male hormone. We measured body composition and energy expenditure. We also analyzed the levels of specific genes and proteins related to fat tissue and energy production. Our findings showed that mice lacking miR-21 had less weight gain in response to male hormones, without fat or brown fat tissue mass changes. They also had reduced energy production, changed eating habits, and altered expression of genes related to fat tissue and energy production. In conclusion, our study suggests that miR-21 in brown fat tissue may regulate the energy imbalance caused by male hormones in PCOS. Adjusting miR-21 levels in brown fat tissue could be a new way to address the metabolic issues associated with PCOS. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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47. Mouse vascularized adipose spheroids: an organotypic model for thermogenic adipocytes.
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Ingeborg Davidsen, Laura, Hagberg, Carolina E., Goitea, Victor, Meinild Lundby, Stine, Larsen, Steen, Frendø Ebbesen, Morten, Stanic, Natasha, Topel, Hande, and Kornfeld, Jan-Wilhelm
- Subjects
WHITE adipose tissue ,MICROPHYSIOLOGICAL systems ,BROWN adipose tissue ,ADIPOSE tissues ,FAT cells ,ENERGY metabolism ,TISSUE scaffolds ,GENE expression ,ADIPOGENESIS - Abstract
Adipose tissues, particularly beige and brown adipose tissue, play crucial roles in energy metabolism. Brown adipose tissues' thermogenic capacity and the appearance of beige cells within white adipose tissue have spurred interest in their metabolic impact and therapeutic potential. Brown and beige fat cells, activated by environmental factors like cold exposure or by pharmacology, share metabolic mechanisms that drive non-shivering thermogenesis. Understanding these two cell types requires advanced, yet broadly applicable in vitro models that reflect the complex microenvironment and vasculature of adipose tissues. Here we present mouse vascularized adipose spheroids of the stromal vascular microenvironment from inguinal white adipose tissue, a tissue with 'beiging' capacity in mice and humans. We show that adding a scaffold improves vascular sprouting, enhances spheroid growth, and upregulates adipogenic markers, thus reflecting increased adipocyte maturity. Transcriptional profiling via RNA sequencing revealed distinct metabolic pathways upregulated in our vascularized adipose spheroids, with increased expression of genes involved in glucose metabolism, lipid metabolism, and thermogenesis. Functional assessment demonstrated increased oxygen consumption in vascularized adipose spheroids compared to classical 2D cultures, which was enhanced by β-adrenergic receptor stimulation correlating with elevated b-adrenergic receptor expression. Moreover, stimulation with the naturally occurring adipokine, FGF21, induced Ucp1 mRNA expression in the vascularized adipose spheroids. In conclusion, vascularized inguinal white adipose tissue spheroids provide a physiologically relevant platform to study how the stromal vascular microenvironment shapes adipocyte responses and influence activated thermogenesis in beige adipocytes. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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48. [18F]F-AraG imaging reveals association between neuroinflammation and brown- and bone marrow adipose tissue.
- Author
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Levi, Jelena, Guglielmetti, Caroline, Henrich, Timothy J., Yoon, John C., Gokhale, Prafulla C., Reardon, David A., Packiasamy, Juliet, Huynh, Lyna, Cabrera, Hilda, Ruzevich, Marisa, Blecha, Joseph, Peluso, Michael J., Huynh, Tony L., An, Sung-Min, Dornan, Mark, Belanger, Anthony P., Nguyen, Quang-Dé, Seo, Youngho, Song, Hong, and Chaumeil, Myriam M.
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BONE marrow , *BROWN adipose tissue , *ADIPOSE tissues , *NEUROINFLAMMATION , *NERVOUS system , *METABOLIC disorders - Abstract
Brown and brown-like adipose tissues have attracted significant attention for their role in metabolism and therapeutic potential in diabetes and obesity. Despite compelling evidence of an interplay between adipocytes and lymphocytes, the involvement of these tissues in immune responses remains largely unexplored. This study explicates a newfound connection between neuroinflammation and brown- and bone marrow adipose tissue. Leveraging the use of [18F]F-AraG, a mitochondrial metabolic tracer capable of tracking activated lymphocytes and adipocytes simultaneously, we demonstrate, in models of glioblastoma and multiple sclerosis, the correlation between intracerebral immune infiltration and changes in brown- and bone marrow adipose tissue. Significantly, we show initial evidence that a neuroinflammation-adipose tissue link may also exist in humans. This study proposes the concept of an intricate immuno-neuro-adipose circuit, and highlights brown- and bone marrow adipose tissue as an intermediary in the communication between the immune and nervous systems. Understanding the interconnectedness within this circuitry may lead to advancements in the treatment and management of various conditions, including cancer, neurodegenerative diseases and metabolic disorders. A mitochondrial PET tracer, [18F]FAraG, enabled visualization of a cooccurrence of neuroinflammation and metabolic changes in brown- and bone marrow adipose tissue in glioblastoma and multiple sclerosis models, as well as in post-acute COVID subjects. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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49. Transcriptomic analysis reveals the effects of maternal exposure to bisphenol AF on hypothalamic development in male neonatal mice.
- Author
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Lv, Lin, Li, Yuanyuan, Chen, Xuanyue, and Qin, Zhanfen
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HYPOTHALAMUS , *MATERNAL exposure , *WHITE adipose tissue , *BROWN adipose tissue , *RNA analysis , *TRANSCRIPTOMES - Abstract
• Maternal exposure to BPAF leads to developmentally relevant transcriptomic changes in the hypothalamus of neonatal mice. • Low-dose BPAF induces the browning of white adipose tissue. • Effects of BPAF on hypothalamic gene expression and white adipose tissue browning was dose-independent. Fragmented data suggest that bisphenol AF (BPAF), a chemical widely used in a variety of products, might have potential impacts on the hypothalamus. Here, we employed male neonatal mice following maternal exposure to explore the effects of low-dose BPAF on hypothalamic development by RNA-sequencing. We found that maternal exposure to approximately 50 µg/(kg·day) BPAF from postanal day (PND) 0 to PND 15 altered the hypothalamic transcriptome, primarily involving the pathways and genes associated with extracellular matrix (ECM) and intercellular adhesion, neuroendocrine regulation, and neurological processes. Further RNA analysis confirmed the changes in the expression levels of concerned genes. Importantly, we further revealed that low-dose BPAF posed a stimulatory impact on pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus and induced the browning of inguinal white adipose tissue. All findings indicate that developmental exposure to low-dose BPAF could interfere with hypothalamic development and thereby lead to alterations in the metabolism. Interestingly, 5000 µg/(kg·day) BPAF caused slighter, non-significant or even inverse alterations than the low dose of 50 µg/(kg·day), displaying a dose-independent effect. Further observations suggest that the the dose-independent effects of BPAF might be associated with oxidative stress and inflammatory responses caused by the high dose. Overall, our study highlights a risk of low-dose BPAF to human neuroendocrine regulation and metabolism. [Display omitted] [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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50. AGPAT3 deficiency impairs adipocyte differentiation and leads to a lean phenotype in mice.
- Author
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Hongyi Zhou, Fick, Kendra, Patel, Vijay, Hilton, Lisa Renee, Ha Won Kim, Zsolt Bagi, Weintraub, Neal L., and Weiqin Chen
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ADIPOGENESIS , *BROWN adipose tissue , *DRINKING (Physiology) , *FAT cells , *ADIPOSE tissues , *PEROXISOME proliferator-activated receptors , *GROWTH disorders - Abstract
Acylglycerophosphate acyltransferases (AGPATs) catalyze the de novo formation of phosphatidic acid to synthesize glycerophospholipids and triglycerides. AGPATs demonstrate unique physiological roles despite a similar biochemical function. AGPAT3 is highly expressed in the testis, kidney, and liver, with intermediate expression in adipose tissue. Loss of AGPAT3 is associated with reproductive abnormalities and visual dysfunction. However, the role of AGPAT3 in adipose tissue and whole body metabolism has not been investigated. We found that male Agpat3 knockout (KO) mice exhibited reduced body weights with decreased white and brown adipose tissue mass. Such changes were less pronounced in the female Agpat3-KO mice. Agpat3-KO mice have reduced plasma insulin growth factor 1 (IGF1) and insulin levels and diminished circulating lipid metabolites. They manifested intact glucose homeostasis and insulin sensitivity despite a lean phenotype. Agpat3-KO mice maintained an energy balance with normal food intake, energy expenditure, and physical activity, except for increased water intake. Their adaptive thermogenesis was also normal despite reduced brown adipose mass and triglyceride content. Mechanistically, Agpat3 was elevated during mouse and human adipogenesis and enriched in adipocytes. Agpat3-knockdown 3T3-L1 cells and Agpat3-deficient mouse embryonic fibroblasts (MEFs) have impaired adipogenesis in vitro. Interestingly, pioglitazone treatment rescued the adipogenic deficiency in Agpat3-deficient cells. We conclude that AGPAT3 regulates adipogenesis and adipose development. It is possible that adipogenic impairment in Agpat3-deficient cells potentially leads to reduced adipose mass. Findings from this work support the unique role of AGPAT3 in adipose tissue. NEW & NOTEWORTHY AGPAT3 deficiency results in male-specific growth retardation. It reduces adipose tissue mass but does not significantly impact glucose homeostasis or energy balance, except for influencing water intake in mice. Like AGPAT2, AGPAT3 is upregulated during adipogenesis, potentially by peroxisome proliferator-activated receptor gamma (PPARc). Loss of AGPAT3 impairs adipocyte differentiation, which could be rescued by pioglitazone. Overall, AGPAT3 plays a significant role in regulating adipose tissue mass, partially involving its influence on adipocyte differentiation. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
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