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Therapies based on mesenchymal stromal cells (MSCs) have become one of the most significant advancements in veterinary regenerative medicine. The isolation of MSCs is usually performed by enzymatic digestion and requires variable times for cell expansion. In addition, these procedures need to be performed in specialized laboratory facilities. An alternative approach to in vitro-expanded MSC therapy is the use of microfragmented adipose tissue (microfat), which is a rich source of cells and growth factors from the stromal vascular fraction. Recent clinical studies support its safety and efficacy in the treatment of musculoskeletal disorders and wound healing. The aim of the present work was to characterize the microfragmented adipose tissue obtained by a new mechanical device, which provides sterile tissue that is ready for use in the clinic by the veterinarian, avoiding the need for specialized laboratory facilities. Microfat-derived MSCs were compared with enzymatically isolated MSCs in terms of their phenotypic characterization, growth rate and differentiation potential. Conditioned medium derived from microfat culture was evaluated for its ability to promote MSC vitality. No differences were observed between MSCs obtained through mechanical fragmentation and those derived from collagenase digestion of adipose tissue, suggesting that the device could serve as a practical source of microfragmented adipose tissue for use in veterinary clinics. [ABSTRACT FROM AUTHOR]

The ongoing obesity epidemic has raised awareness of the complex physiology of adipose tissue. Abnormal adipocyte differentiation results in the development of systemic metabolic disorders such as insulin resistance and diabetes. The conjugation of NEDD8 (neural precursor cell expressed, developmentally downregulated 8) to target protein, termed neddylation, has been shown to mediate adipogenesis. However, much remains unknown about its role in adipogenesis. Here, we demonstrated that neddylation and its targets, the cullin (CUL) family members, are differentially regulated during mouse and human adipogenesis. Inhibition of neddylation by MLN4924 significantly reduced adipogenesis of 3T3-L1 and human stromal vascular cells. Deletion of NAE1, a subunit of the only NEDD8 E1 enzyme, suppressed neddylation and impaired adipogenesis. Neddylation deficiency did not affect mitotic cell expansion. Instead, it disrupted CREB/CEBPβ/PPARγ signaling, essential for adipogenesis. Interestingly, among the neddylation-targeted CUL family members, deletion of CUL3, but not CUL1, CUL2, or CUL4A, largely replicated the adipogenic defects observed with neddylation deficiency. A PPARγ agonist minimally rescued the adipogenic defects caused by the deletion of NAE1 and CUL3. In conclusion, our study demonstrates that neddylation and its targeted CUL3 are crucial for adipogenesis. These findings provide potential targets for therapeutic intervention in obesity and metabolic disorders. [ABSTRACT FROM AUTHOR]

• Better diet quality had a direct (beneficial) effect on pain. • Higher consumption of core foods was related to less pain in women, but not men. • Adiposity did not mediate the relationship between diet quality and pain. • Strategies for pain management should consider diet quality. Dietary intake has been associated with pain and physical function, but it is unclear if these relationships are mediated by adiposity. Data were derived from the Whyalla Intergenerational Study of Health (n = 654, 57% women). Structural equation modelling tested the hypotheses that adiposity (body mass index (BMI), waist circumference (WC), or body fat (BF, dual energy x-ray absorptiometry)) would mediate the relationship between diet quality (Dietary Guideline Index (DGI) total, core, or non-core scores) and pain (Short Form-36 bodily pain scale (SF36-BPS)), or physical function (grip-strength), overall, and by gender. Adiposity did not mediate a relationship between DGI scores and pain. Direct effects were observed between DGI total scores and SF36-BPS accounting for BMI (β = 0.170, 95% CI 0.002, 0.339), and between DGI core food scores and SF36-BPS (BMI, β = 0.278, 95% CI 0.070, 0.486; WC, β = 0.266, 95% CI 0.058, 0.474; BF, β = 0.266, 95% CI 0.060, 0.473). In women, direct effects existed between DGI scores and SF36-BPS (DGI total scores, BMI, β = 0.388, 95% CI 0.162, 0.613; WC, β = 0.372, 95% CI 0.146, 0.598; BF, β = 0.382, 95% CI 0.158, 0.605, and DGI core scores, BMI, β = 0.482, 95% CI 0.208, 0.757; WC, β = 0.472, 95% CI 0.197, 0.747; BF, β = 0.467, 95% CI 0.195, 0.739), and DGI total scores and grip-strength (BMI, β = 0.075, 95% CI 0.008, 0.142; WC, β = 0.076, 95% CI 0.009, 0.143; BF, β = 0.079, 95% CI 0.011, 0.146). Better diet quality is associated with lower bodily pain, irrespective of adiposity. Findings highlight the potential role of diet quality in pain management and function, particularly in women. A cross-sectional study of 654 Australian adults (57% women) from the WISH found better diet quality, particularly the intake of core foods, assessed via the DGI, was associated with lower body pain. These findings were most pronounced in women. Mediation analyses did not show any influence of adiposity in this relationship. Abbreviations: BMI, body mass index; DGI, Dietary Guideline Index; WISH, Whyalla Intergenerational Study of Health. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: One of the main features of polycystic ovary syndrome (PCOS) is increased adipose tissue, which can result in hormonal disturbances. In the present study, we aimed to investigate which indicator of obesity could better associate with hormonal disturbances in PCOS women. Methods: In this cross-sectional analysis, women with PCOS were included according to the Rotterdam criteria. Fasting blood samples were analyzed for biochemical, metabolic, and hormonal parameters. Anthropometric measures comprised body composition indices (assessed by bioelectric impedance analysis [BIA]), waist circumference, body mass index (BMI), and waist-to-height ratio (WHtR). Linear regression modeling was used to assess the association between anthropometric indices and hormonal imbalance, adjusted for age, mensuration status, and the homeostasis model assessment-estimated insulin resistance (HOMA-IR). Receiver operating characteristics (ROC) curves were utilized to ascertain the sensitivity, specificity, and optimal cut-off points of various anthropometric indices in identifying hyperandrogenism. Results: A total of 129 PCOS women with a median (interquartile range [IQR]) age of 32.0 (23.0–32.0) years and a median BMI of 26.3 (23.00-29.70) kg/m2 were enrolled. In the adjusted linear regression model, BMI (β = 0.053, P < 0.001), waist circumference (β = 0.021, P = 0.001), WHtR (β = 3.325, P = 0.002), total fat mass (β = 0.021, P = 0.002), trunk fat mass (β = 0.038, P = 0.006), and leg fat mass (β = 0.045, P = 0.004) were positively associated with free androgen index (FAI). In addition, BMI (β=−0.017, P = 0.003), waist circumference (β=−0.008, P = 0.002), WHtR (β=−1.167, P = 0.004), total fat mass (β=−0.008, P=0.003), trunk fat mass (β=−0.017, P=0.001), and leg fat mass (β=−0.018, P=0.004) were negatively associated with the serum level of sex hormone binding globulin (SHBG). WHtR showed the greatest area under the curve (AUC) value (AUC = 0.676, P = 0.001) for identifying hyperandrogenism (FAI ≥ 4.97 or total testosterone ≥ 0.7 ng/mL) in PCOS women with corresponding sensitivity of 87.30% and specificity of 39.70%. Conclusions: WHtR is related to hyperandrogenism in PCOS better than other anthropometric measures. [ABSTRACT FROM AUTHOR]

Cell identities are defined by intrinsic transcriptional networks and spatio-temporal environmental factors. Here, we explored multiple factors that contribute to the identity of adipose stem cells, including anatomic location, microvascular neighborhood, and sex. Our data suggest that adipose stem cells serve a dual role as adipocyte precursors and fibroblast-like cells that shape the adipose tissue's extracellular matrix in an organotypic manner. We further find that adipose stem cells display sexual dimorphism regarding genes involved in estrogen signaling, homeobox transcription factor expression and the renin-angiotensin-aldosterone system. These differences could be attributed to sex hormone effects, developmental origin, or both. Finally, our data demonstrate that adipose stem cells are distinct from mural cells, and that the state of commitment to adipogenic differentiation is linked to their anatomic position in the microvascular niche. Our work supports the importance of sex and microvascular function in adipose tissue physiology. Several factors contribute to the identity of adipose stem cells, including anatomic location, microvascular neighborhood and sex. Here, authors find that adipose stem cells are sexual dimorphic cells with dual roles as preadipocytes and fibroblasts. [ABSTRACT FROM AUTHOR]

Although evidence suggests that intramuscular fat infiltration may influence muscle strength, the precise mechanisms remain unclear. This study aimed to determine whether intramuscular fat infiltration affects muscle mechanical properties during contraction and whether these mechanical properties mediate the relationship between intramuscular fat infiltration and muscle strength. Seventy-nine healthy older women aged 75.1 ± 6.8 years were included in this study. The echo intensity (EI) of the vastus lateralis (VL) was measured as an intramuscular fat infiltration index using B-mode ultrasonography. Maximum voluntary isometric contraction strength (MVIC) was assessed using a dynamometer. The VL shear elastic modulus (G), a mechanical property index, was measured using ultrasound shear wave elastography under various muscle contraction conditions, at rest and at 15%, 30%, and 45% MVIC (G0, G15, G30, and G45). To evaluate the degree of increase in the shear elastic modulus with increasing muscle contraction intensity, the slope of the regression line (Gslope) between muscle contraction and shear elastic modulus was calculated for each participant. The results showed that EI was significantly associated with G30 and G45 but not with G0 or G15. The EI can significantly explain the inter-individual differences in Gslope. Mediation analysis revealed that the effect of EI on MVIC through Gslope was significant (indirect effect = −0.31, 95% confidence interval (−0.57, −0.12)). These findings suggest that a greater EI is associated with a lower G during muscle contraction. Furthermore, our results show that the relationship between EI and MVIC is mediated by Gslope. [ABSTRACT FROM AUTHOR]

The rising prevalence of obesity is a grave public health threat. In response to excessive energy intake, adipocyte hypertrophy impairs cellular function and leads to metabolic dysfunctions while de novo adipogenesis leads to healthy adipose tissue expansion. Through burning fatty acids and glucose, the thermogenic activity of brown/beige adipocytes can effectively reduce the size of adipocytes. Recent studies show that retinoids, especially retinoic acid (RA), promote adipose vascular development which in turn increases the number of adipose progenitors surrounding the vascular vessels. RA also promotes preadipocyte commitment. In addition, RA promotes white adipocyte browning and stimulates the thermogenic activity of brown/beige adipocytes. Thus, vitamin A is a promising anti-obesity micronutrient. [ABSTRACT FROM AUTHOR]

Obesity during pregnancy has been escalating, becoming a huge problem that poses consequences not only for the health of the offspring but also for the maternal well-being. Women's adipose and hepatic tissue metabolism undergoes significant changes during the gestational period. During pregnancy, obesity is a primary instigator of steatosis, increasing the risk of non-alcholic fatty liver disease (NAFLD), now recognized under the updated nomenclature metabolic dysfunction-associated steatotic liver disease (MASLD). Pregnant women with obesity present higher levels of free fatty acids and glucose, reduction in insulin sensitivity, and adipose tissue endocrine dysregulation. Furthermore, obesity-induced modifications in clock genes and lipid-associated gene expression within adipose tissue disrupt crucial metabolic adaptations, potentially culminating in adipose tissue dysfunction. Thus, the liver experiences increased exposure to free fatty acids through the portal vein. Higher uptake of free fatty acids into the liver disrupts hepatic lipid oxidation while enhances lipogenesis, thereby predisposing to ectopic fat deposition within the liver. This review focuses on the obesity-induced changes during pregnancy in both liver and adipose tissue metabolism, elucidating how the metabolic crosstalk between these two organs can be dysregulated in pregnant women living with obesity. [ABSTRACT FROM AUTHOR]

The modulation of cellular phenotypes within adipose tissue provides a potential means for therapeutic intervention for diabetes. Endogenous interleukin-10 (IL-10) protects against diet-induced insulin resistance. We examined the effects and mechanisms of action of IL-10-treated adipose-derived stromal cells on diabetes-induced insulin resistance and liver gluconeogenesis. We harvested stromal vascular fractions (SVFs) from the adipose tissue of diabetic (Leprdb/db) mice and treated them with IL-10 in vitro. SVFs treated with 10 or 100 ng of IL-10 were injected into the inguinal adipose tissue of Leprdb/db mice. IL-10 treatment suppressed the mRNA expression of IL-6, IL-33, CCL2, TNF-α, and IL-1β. Additionally, it suppressed the protein expression of IL-6, pmTOR, pJNK, and pNF-κB but enhanced Foxp3 mRNA expression in SVFs from diabetic mice. Meanwhile, IL-10 treatment repressed CCL2 and PDGFRα expression in adipose tissue macrophages (ATMs) and IL-6 expression in non-ATMs but increased the Foxp3 and IL-10 mRNA expression of ATMs from diabetic mice. Injection of IL-10-treated SVFs decreased the IL-6, IL-33, CCL2, IL-1β, and CCL2 but enhanced the Foxp3 and IL-10 mRNA expression of adipose tissue from Leprdb/db mice. Furthermore, injection of IL-10-treated SVFs increased CD4+ regulatory T cells (Tregs) in SVFs and adipose IL-10 levels and suppressed plasma adiponectin levels and DPP4 activity in diabetic mice. Injection of IL-10-treated SVFs decreased hepatic G6PC and PCK1 mRNA expression and increased Akt activation, STAT3 phosphorylation in the liver, and glucose tolerance in diabetic mice. Our data suggest that IL-10 treatment decreases inflammation in adipose SVFs of diabetic mice. Injection of IL-10-treated SVFs into the adipose tissue decreased diabetes-induced gluconeogenesis gene expression, DPP4 activity, and insulin resistance by enhancing Treg cells in diabetic mice. These data suggest that IL-10-treated adipose stromal vascular cells could be a promising therapeutic strategy for diabetes mellitus. [ABSTRACT FROM AUTHOR]

White adipose tissue (WAT) makes up about 20–25% of total body mass in healthy individuals and is crucial for regulating various metabolic processes, including energy metabolism, endocrine function, immunity, and reproduction. In adipose tissue research, "adipogenesis" is commonly used to refer to the process of adipocyte formation, spanning from stem cell commitment to the development of mature, functional adipocytes. Although, this term should encompass a wide range of processes beyond commitment and differentiation, to also include other stages of adipose tissue development such as hypertrophy, hyperplasia, angiogenesis, macrophage infiltration, polarization, etc.... collectively, referred to herein as the adipogenic cycle. The term "differentiation", conversely, should only be used to refer to the process by which committed stem cells progress through distinct phases of subsequent differentiation. Recognizing this distinction is essential for accurately interpreting research findings on the mechanisms and stages of adipose tissue development and function. In this review, we focus on the molecular regulation of white adipose tissue development, from commitment to terminal differentiation, and examine key functional aspects of WAT that are crucial for normal physiology and systemic metabolic homeostasis. [ABSTRACT FROM AUTHOR]

Background: Personalized medicine, an emerging approach, considers individual differences to tailor treatments optimally. Persian medicine (PM) incorporates individual differences through Mizāj (temperament). A comprehensive understanding of each Mizaj type's characteristics is essential in designing standardized diagnostic tools. Objectives: This study aims to explore the attributes of one of the most significant Mizaj groups, namely cold-wet Mizaj, and its subtypes, including cold-wet Su-e-Mizaj (dystemperament), as well as phlegm dominance in PM sources. Methods: Persian medicine literature, including the Canon of Medicine, was reviewed for relevant concepts. Reliable scientific databases, including PubMed, Scopus, and MagIran, were searched using keywords such as Mizaj, temperament, Su-e-Mizaj, dystemperament, cold-wet dystemperament, phlegm, and Balgham. The obtained results were studied and categorized. Results: Out of the 196 articles obtained related to Mizaj, 16 investigated indices. No studies were found on the indices of coldwet Mizaj and phlegm dominance separately. PM sources exhibit high congruence in describing the characteristics of cold-wet Mizaj. Specifically, emphasis is placed on characteristics such as coldness and softness of the skin to the touch, high fat mass, pale and white complexion, excessive body secretions, weakness and slowness of physical and physiological actions, low vitality, timidity, poor memory, and slow-wittedness. In cold-wet dystemperament, symptoms are more severe, and in the presence of phlegm, a feeling of heaviness is also mentioned as a specific symptom. Conclusions: By compiling indices of cold-wet Mizaj/dystemperament and phlegm dominance, this study can contribute to the development of standardized PM questionnaires, facilitating a personalized approach to the diagnosis and treatment of diseases. [ABSTRACT FROM AUTHOR]

Background: Scientific evidence highlights the influence of biological sex on the relationship between stress and metabolic dysfunctions. However, there is limited understanding of how diet and stress concurrently contribute to metabolic dysregulation in both males and females. Our study aimed to investigate the combined effects of high-fat diet (HFD) induced obesity and repeated stress on fear-related behaviors, metabolic, immune, and hypothalamic outcomes in male and female mice. Methods: To investigate this, we used a highly reliable rodent behavioral model that faithfully recapitulates key aspects of post-traumatic stress disorder (PTSD)-like fear. We subjected mice to footshock stressor followed by a weekly singular footshock stressor or no stressor for 14 weeks while on either an HFD or chow diet. At weeks 10 and 14 we conducted glucose tolerance and insulin sensitivity measurements. Additionally, we placed the mice in metabolic chambers to perform indirect calorimetric measurements. Finally, we collected brain and peripheral tissues for cellular analysis. Results: We observed that HFD-induced obesity disrupted fear memory extinction, increased glucose intolerance, and affected energy expenditure specifically in male mice. Conversely, female mice on HFD exhibited reduced respiratory exchange ratio (RER), and a significant defect in glucose tolerance only when subjected to repeated stress. Furthermore, the combination of repeated stress and HFD led to sex-specific alterations in proinflammatory markers and hematopoietic stem cells across various peripheral metabolic tissues. Single-nuclei RNA sequencing (snRNAseq) analysis of the ventromedial hypothalamus (VMH) revealed microglial activation in female mice on HFD, while male mice on HFD exhibited astrocytic activation under repeated stress. Conclusions: Overall, our findings provide insights into complex interplay between repeated stress, high-fat diet regimen, and their cumulative effects on health, including their potential contribution to the development of PTSD-like stress and metabolic dysfunctions, emphasizing the need for further research to fully understand these interconnected pathways and their implications for health. Plain Language Summary: In our study, we attempted to investigate how the combination of diet, stress, and sex can affect various aspects of health in mice. Specifically, we aimed to elucidate the neurobiology of underlying stress and metabolic dysfunction with a focus on sex-specific differences. We recognize that stress and metabolic disorders often co-occur and exhibit distinct patterns between sexes. In the present study, we observed that male mice fed a high-fat diet exhibited an inability to extinguish fear memory, mirroring a hallmark symptom observed in PTSD patients. We also observed sex-specific differences in metabolic and immune function in response to the diet and stress challenge. We uncovered that both repeated stress and a HFD can induce alterations in the quantity and types of immune cells present in various peripheral tissues, suggesting potential pathways through which metabolic diseases may develop. Our investigation further revealed that the ventromedial hypothalamus, responsible for regulating metabolism and stress behavior, exhibited distinct transcriptomic activity patterns in males and females. These findings shed light on the complex connections between high fat diet, stress levels, and overall health, emphasizing the importance of continued research in this area. Highlights: Fourteen weeks of high fat diet (HFD) impaired fear memory extinction in stressed male mice but not in female mice. Female mice demonstrated HFD-induced glucose intolerance only under repeated stress conditions. Male mice on HFD showed an increase in energy expenditure and glucose intolerance, while female mice on HFD showed decreased respiratory exchange ratio (RER). Furthermore, male mice on HFD showed decreased bone marrow progenitor cells, increased neutrophils in gonadal adipose tissue, decreased neutrophils in the aorta, and increased macrophages in the heart compared to female mice. Single nuclei RNA sequencing (snRNAseq) analysis of the ventromedial hypothalamus revealed differential microglial and astrocytic cell activation in female and male mice respectively, with females showing elevated expression of Hcrt and Pmch, while males showing increased expression of Gfap and Pomc. Together, these findings indicate distinct patterns in fear memory extinction, metabolic parameters, immune cell distribution, and gene expression within the ventromedial hypothalamus. [ABSTRACT FROM AUTHOR]

Background: C16:0 and cis-9 C18:1 may have different effects on animal growth and health due to unique metabolism in vivo. This study was investigated to explore the different effects of altering the ratio of C16:0 and cis-9 C18:1 in fat supplements on growth performance, lipid metabolism, intestinal barrier, cecal microbiota, and inflammation in fattening bulls. Thirty finishing Angus bulls (626 ± 69 kg, 21 ± 0.5 months) were divided into 3 treatments according to the randomized block design: (1) control diet without additional fat (CON), (2) CON + 2.5% palmitic acid calcium salt (PA, 90% C16:0), and (3) CON + 2.5% mixed fatty acid calcium salt (MA, 60% C16:0 + 30% cis-9 C18:1). The experiment lasted for 104 d, after which all the bulls were slaughtered and sampled for analysis. Results: MA tended to reduce 0–52 d dry matter intake compared to PA (DMI, P = 0.052). Compared with CON and MA, PA significantly increased 0–52 d average daily gain (ADG, P = 0.027). PA tended to improve the 0–52 d feed conversion rate compared with CON (FCR, P = 0.088). Both PA and MA had no significant effect on 52–104 days of DMI, ADG and FCR (P > 0.05). PA tended to improve plasma triglycerides compared with MA (P = 0.077), significantly increased plasma cholesterol (P = 0.002) and tended to improve subcutaneous adipose weight (P = 0.066) when compared with CON and MA. Both PA and MA increased visceral adipose weight compared with CON (P = 0.021). Only PA increased the colonization of Rikenellaceae, Ruminococcus and Proteobacteria in the cecum, and MA increased Akkermansia abundance (P < 0.05). Compared with CON, both PA and MA down-regulated the mRNA expression of Claudin-1 in the jejunum (P < 0.001), increased plasma diamine oxidase (DAO, P < 0.001) and lipopolysaccharide (LPS, P = 0.045). Compared with CON and MA, PA down-regulated the ZO-1 in the jejunum (P < 0.001) and increased plasma LPS-binding protein (LBP, P < 0.001). Compared with CON, only PA down-regulated the Occludin in the jejunum (P = 0.013). Compared with CON, PA and MA significantly up-regulated the expression of TLR-4 and NF-κB in the visceral adipose (P < 0.001) and increased plasma IL-6 (P < 0.001). Compared with CON, only PA up-regulated the TNF-α in the visceral adipose (P = 0.01). Compared with CON and MA, PA up-regulated IL-6 in the visceral adipose (P < 0.001), increased plasma TNF-α (P < 0.001), and reduced the IgG content in plasma (P = 0.035). Compared with CON, PA and MA increased C16:0 in subcutaneous fat and longissimus dorsi muscle (P < 0.05), while more C16:0 was also deposited by extension and desaturation into C18:0 and cis-9 C18:1. However, neither PA nor MA affected the content of cis-9 C18:1 in longissimus dorsi muscle compared with CON (P > 0.05). Conclusions: MA containing 30% cis-9 C18:1 reduced the risk of high C16:0 dietary fat induced subcutaneous fat obesity, adipose tissue and systemic low-grade inflammation by accelerating fatty acid oxidative utilization, improving colonization of Akkermansia, reducing intestinal barrier damage, and down-regulating NF-κB activation. [ABSTRACT FROM AUTHOR]

Summary: Dietary patterns are closely related to obesity, and a balanced diet can prevent obesity more than a single food or nutrient. In this study, we investigated the anti‐obesity effects of food and medicine homologous ingredient complex (FMHIC). The serum biochemical indices related to lipid metabolism were significantly improved in the FMHIC group. Meanwhile, it significantly inhibited the accumulation of lipid droplets, improved adipocyte hypertrophy and downregulated gene expression related to lipid production. FMHIC can effectively regulate intestinal flora richness and structural disorder in obese mice and result in a higher abundance of NK4A214_group and Prevotellaceae _UCG_001, and a lower abundance of Negativibacillus, Lachnospiraceae_NK4A136_group, Lachnoclostridium and GCA_900066575. Spearman correlation analysis showed that there was a strong correlation between species richness and lipid metabolism and that FMHIC might adjust lipid metabolism by regulating the abundance of intestinal flora. In conclusion, FMHIC regulates lipid metabolism and modulates gut microbiota to regulate high‐fat diet‐induced dysbiosis. [ABSTRACT FROM AUTHOR]

While obesity-related nonalcoholic fatty liver disease (NAFLD) is linked with metabolic dysfunctions such as insulin resistance and adipose tissue inflammation, lean NAFLD more often progresses to liver fibrosis even in the absence of metabolic syndrome. This review aims to summarize the current knowledge regarding the mechanisms of liver fibrosis in lean NAFLD. The most commonly used lean NAFLD models include a methionine/choline-deficient (MCD) diet, a high-fat diet with carbon tetrachloride (CCl4), and a high-fructose and high-cholesterol diet. The major pro-fibrogenic mechanisms in lean NAFLD models include increased activation of the extracellular signal-regulated kinase (ERK) pathway, elevated expression of α-smooth muscle actin (α-SMA), collagen type I, and TGF-β, and modulation of fibrogenic markers such as tenascin-X and metalloproteinase inhibitors. Additionally, activation of macrophage signaling pathways promoting hepatic stellate cell (HSC) activation further contributes to fibrosis development. Animal models cannot cover all clinical features that are evident in patients with lean or obese NAFLD, implicating the need for novel models, as well as for deeper comparisons of clinical and experimental studies. Having in mind the prevalence of fibrosis in lean NAFLD patients, by addressing specific pathways, clinical studies can reveal new targeted therapies along with novel biomarkers for early detection and enhancement of clinical management for lean NAFLD patients. [ABSTRACT FROM AUTHOR]

Adipose tissue, a central player in energy balance, exhibits significant metabolic flexibility that is often compromised in obesity and type 2 diabetes (T2D). Mitochondrial dysfunction within adipocytes leads to inefficient lipid handling and increased oxidative stress, which together promote systemic metabolic disruptions central to obesity and its complications. This review explores the pivotal role that mitochondria play in altering the metabolic functions of the primary adipocyte types, white, brown, and beige, within the context of obesity and T2D. Specifically, in white adipocytes, these dysfunctions contribute to impaired lipid processing and an increased burden of oxidative stress, worsening metabolic disturbances. Conversely, compromised mitochondrial function undermines their thermogenic capabilities, reducing the capacity for optimal energy expenditure in brown adipocytes. Beige adipocytes uniquely combine the functional properties of white and brown adipocytes, maintaining morphological similarities to white adipocytes while possessing the capability to transform into mitochondria-rich, energy-burning cells under appropriate stimuli. Each type of adipocyte displays unique metabolic characteristics, governed by the mitochondrial dynamics specific to each cell type. These distinct mitochondrial metabolic phenotypes are regulated by specialized networks comprising transcription factors, co-activators, and enzymes, which together ensure the precise control of cellular energy processes. Strong evidence has shown impaired adipocyte mitochondrial metabolism and faulty upstream regulators in a causal relationship with obesity-induced T2D. Targeted interventions aimed at improving mitochondrial function in adipocytes offer a promising therapeutic avenue for enhancing systemic macronutrient oxidation, thereby potentially mitigating obesity. Advances in understanding mitochondrial function within adipocytes underscore a pivotal shift in approach to combating obesity and associated comorbidities. Reigniting the burning of calories in adipose tissues, and other important metabolic organs such as the muscle and liver, is crucial given the extensive role of adipose tissue in energy storage and release. [ABSTRACT FROM AUTHOR]

RNA splicing dysregulation and the involvement of specific splicing factors are emerging as common factors in both obesity and metabolic disorders. The study provides compelling evidence that the absence of the splicing factor SRSF1 in mature adipocytes results in whitening of brown adipocyte tissue (BAT) and impaired thermogenesis, along with the inhibition of white adipose tissue browning in mice. Combining single‐nucleus RNA sequencing with transmission electron microscopy, it is observed that the transformation of BAT cell types is associated with dysfunctional mitochondria, and SRSF1 deficiency leads to degenerated and fragmented mitochondria within BAT. The results demonstrate that SRSF1 effectively binds to constitutive exon 6 of Ndufs3 pre‐mRNA and promotes its inclusion. Conversely, the deficiency of SRSF1 results in impaired splicing of Ndufs3, leading to reduced levels of functional proteins that are essential for mitochondrial complex I assembly and activity. Consequently, this deficiency disrupts mitochondrial integrity, ultimately compromising the thermogenic capacity of BAT. These findings illuminate a novel role for SRSF1 in influencing mitochondrial function and BAT thermogenesis through its regulation of Ndufs3 splicing within BAT. [ABSTRACT FROM AUTHOR]

By 2060, an estimated one in four Americans will be elderly. Consequently, the prevalence of osteoporosis and fragility fractures will also increase. Presently, no available intervention definitively prevents or manages osteoporosis. This study explores whether Pool 7 Compound 3 (P7C3) reduces progressive bone loss and fragility following the onset of ovariectomy (OVX)‐induced osteoporosis. Results confirm OVX‐induced weakened, osteoporotic bone together with a significant gain in adipogenic body weight. Treatment with P7C3 significantly reduced osteoclastic activity, bone marrow adiposity, whole‐body weight gain, and preserved bone area, architecture, and mechanical strength. Analyses reveal significantly upregulated platelet derived growth factor‐BB and leukemia inhibitory factor, with downregulation of interleukin‐1 R6, and receptor activator of nuclear factor kappa‐B (RANK). Together, proteomic data suggest the targeting of several key regulators of inflammation, bone, and adipose turnover, via transforming growth factor‐beta/SMAD, and Wingless‐related integration site/be‐catenin signaling pathways. To the best of the knowledge, this is first evidence of an intervention that drives against bone loss via RANK. Metatranscriptomic analyses of the gut microbiota show P7C3 increased Porphyromonadaceae bacterium, Candidatus Melainabacteria, and Ruminococcaceae bacterium abundance, potentially contributing to the favorable inflammatory, and adipo‐osteogenic metabolic regulation observed. The results reveal an undiscovered, and multifunctional therapeutic strategy to prevent the pathological progression of OVX‐induced bone loss. [ABSTRACT FROM AUTHOR]

Background: Reducing production costs while producing high-quality livestock and poultry products is an ongoing concern in the livestock industry. The addition of oil to livestock and poultry diets can enhance feed palatability and improve growth performance. Emulsifiers can be used as potential feed supplements to improve dietary energy utilization and maintain the efficient productivity of broilers. Therefore, further investigation is warranted to evaluate whether dietary emulsifier supplementation can improve the efficiency of fat utilization in the diet of yellow-feathered broilers. In the present study, the effects of adding emulsifier to the diet on lipid metabolism and the performance of yellow-feathered broilers were tested. A total of 240 yellow-feasted broilers (21-day-old) were randomly divided into 4 groups (6 replicates per group, 10 broilers per replicate, half male and half female within each replicate). The groups were as follows: the control group (fed with basal diet), the group fed with basal diet supplemented with 500 mg/kg emulsifier, the group fed with a reduced oil diet (reduced by 1%) supplemented with 500 mg/kg emulsifier, and the group fed with a reduced oil diet supplemented with 500 mg/kg emulsifier. The trial lasted for 42 days, during which the average daily feed intake, average daily gain, and feed-to-gain ratio were measured. Additionally, the expression levels of lipid metabolism-related genes in the liver, abdominal fat and each intestinal segment were assessed. Results: The results showed that compared with the basal diet group, (1) The average daily gain of the basal diet + 500 mg/kg emulsifier group significantly increased (P < 0.05), and the half-even-chamber rate was significantly increased (P < 0.05); (2) The mRNA expression levels of Cd36, Dgat2, Apob, Fatp4, Fabp2, and Mttp in the small intestine were significantly increased (P < 0.05). (3) Furthermore, liver TG content significantly decreased (P < 0.05), and the mRNA expression level of Fasn in liver was significantly decreased (P < 0.05), while the expression of Apob, Lpl, Cpt-1, and Pparα significantly increased (P < 0.05). (4) The mRNA expression levels of Lpl and Fatp4 in adipose tissue were significantly increased (P < 0.05), while the expression of Atgl was significantly decreased (P < 0.05). (5) Compared with the reduced oil diet group, the half-evading rate and abdominal fat rate of broilers in the reduced oil diet + 500 mg/kg emulsifier group were significantly increased (P < 0.05), and the serum level of LDL-C increased significantly (P < 0.05)0.6) The mRNA expression levels of Cd36, Fatp4, Dgat2, Apob, and Mttp in the small intestine were significantly increased (P < 0.05). 7) The mRNA expression levels of Fasn and Acc were significantly decreased in the liver (P < 0.05), while the mRNA expression levels of Lpin1, Dgat2, Apob, Lpl, Cpt-1, and Pparα were significantly increased (P < 0.05). Conclusions: These results suggest that dietary emulsifier can enhance the fat utilization efficiency of broilers by increasing the small intestinal fatty acid uptake capacity, inhibiting hepatic fatty acid synthesis and promoting hepatic TG synthesis and transport capacity. This study provides valuable insights for the potential use of emulsifier supplementation to improve the performance of broiler chickens. [ABSTRACT FROM AUTHOR]

Introduction: Obesity is a multifactorial disease associated with the development of many comorbidities. This disease is associated with several metabolic alterations; however, it has been shown that some individuals with obesity do not exhibit metabolic syndrome. Adipose tissue neutralizes the detrimental effects of circulating fatty acids, ectopic deposition, and inflammation, among others, through its esterification into neutral lipids that are stored in the adipocyte. However, when the adipocyte is overloaded, i.e., its expansion capacity is exceeded, this protection is lost, resulting in fatty acid toxicity with ectopic fat accumulation in peripheral tissues and inflammation. In this line, this study aimed to investigate whether polymorphisms in genes that control adipose tissue fat storage capacity are potential biomarkers for severe obesity susceptibility and also metabolic complications. Methods: This study enrolled 305 individuals with severe obesity (cases, BMI≥35 kg/m²) and 196 individuals with normal weight (controls, 18.5≤BMI≤24.9 kg/m²). Demographic, anthropometric, biochemical, and blood pressure variables were collected from the participants. Plasma levels of leptin, resistin, MCP1, and PAI1 were measured by Bio-Plex 200 Multiplexing Analyzer System. Genomic DNA was extracted and variants in DBC1 (rs17060940), SIRT1 (rs7895833 and rs1467568), UCP2 (rs660339), PPARG (rs1801282) and ADRB2 (rs1042713 and rs1042714) genes were genotyped by PCR allelic discrimination using TaqMan® assays. Results: Our findings indicated that SIRT1 rs7895833 polymorphism was a risk factor for severe obesity development in the overdominant model. SIRT1 rs1467568 and UCP2 rs660339 were associated with anthropometric traits. SIRT1 rs1467568 G allele was related to lower medians of body adipose index and hip circumference, while the UCP2 rs660339 AA genotype was associate with increased body mass index. Additionally, DBC1 rs17060940 influenced glycated hemoglobin. Regarding metabolic alterations, 27% of individuals with obesity presented balanced metabolic status in our cohort. Furthermore, SIRT1 rs1467568 AG genotype increased 2.5 times the risk of developing metabolic alterations. No statistically significant results were observed with Peroxisome Proliferator-Activated Receptor Gama and ADRB2 polymorphisms. Discussion/Conclusion: This study revealed that SIRT1 rs7895833 and rs1467568 are potential biomarkers for severe obesity susceptibility and the development of unbalanced metabolic status in obesity, respectively. UCP2 rs660339 and DBC1 rs17060940 also showed a significant role in obesity related-traits. [ABSTRACT FROM AUTHOR]

The adipokine chemerin contributes to exercise-induced improvements in glucose and lipid metabolism; however, the underlying mechanism remains unclear. We aimed to confirm the impact of reduced chemerin expression on exercise-induced improvement in glycolipid metabolism in male diabetic (DM) mice through exogenous chemerin administration. Furthermore, the underlying mechanism of chemerin involved in changes in muscle mitochondria function mediated by androgen/androgen receptor (AR) was explored by generating adipose-specific and global chemerin knockout (adipo-chemerin−/− and chemerin−/−) mice. DM mice were categorized into the DM, exercised DM (EDM), and EDM + chemerin supplementation groups. Adipo-chemerin−/− and chemerin−/− mice were classified in the sedentary or exercised groups and fed either a normal or high-fat diet. Exercise mice underwent a 6-wk aerobic exercise regimen. The serum testosterone and chemerin levels, glycolipid metabolism indices, mitochondrial function, and protein levels involved in mitochondrial biogenesis and dynamics were measured. Notably, exogenous chemerin reversed exercise-induced improvements in glycolipid metabolism, AR protein levels, mitochondrial biogenesis, and mitochondrial fusion in DM mice. Moreover, adipose-specific chemerin knockout improved glycolipid metabolism, enhanced exercise-induced increases in testosterone and AR levels in exercised mice, and alleviated the detrimental effects of a high-fat diet on mitochondrial morphology, biogenesis, and dynamics. Finally, similar improvements in glucose metabolism (but not lipid metabolism), mitochondrial function, and mitochondrial dynamics were observed in chemerin−/− mice. In conclusion, decreased chemerin levels affect exercise-induced improvements in glycolipid metabolism in male mice by increasing mitochondrial number and function, likely through changes in androgen/AR signaling. NEW & NOTEWORTHY: Decreased chemerin levels affect exercise-induced improvements in glycolipid metabolism in male mice by increasing mitochondrial number and function, which is likely mediated by androgen/androgen receptor expression. This study is the first to report the regulatory mechanism of chemerin in muscle mitochondria. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the effects of weaning age and pace on blood metabolites, cortisol concentration, and mRNA abundance of inflammation-related genes in Holstein dairy calves. A total of 70 1-d-old calves (38.8 ± 4.4 kg BW ± SD), blocked by sex and birth BW, were randomly assigned to a 2 × 2 factorial arrangement of treatments. The first factor was weaning age, which was either early (6 wk) or late (8 wk). The second factor was weaning pace, which was either abrupt (4 steps down over 3 d; the initial milk replacer was 7.6 L, which was reduced by 1.9 L in each step-down) or gradual (7 steps down over 14 d; the initial milk replacer was 7.6 L, which was reduced by 1.09 L in each step-down), generating early-abrupt (EA), early-gradual (EG), late-abrupt (LA), and late-gradual (LG) treatments. All treatments had 10 female and 8 male calves, except EA that had 1 fewer male calf. Milk replacer (24% CP, 17% fat) was bottle fed, up to 1,200 g/d, twice daily (0600 h and 1800 h). The EA and EG treatment calves received 46.2 kg of milk replacer, and the LA and LG treatment calves received 63 kg of milk replacer. The study had 2 cohorts (2020, n = 40; 2021, n = 31), and each cohort included all treatments. Blood was collected from the jugular vein at 0900 h at 3 and 7 d of age, and a day before starting and a day after weaning completion. Male calves were humanely killed a day after weaning. Rumen, jejunum, large intestine, liver, omental adipose and perirenal adipose tissues were sampled to determine the mRNA abundance of inflammation-related genes. Weaning pace, age, pace × age, birth BW, and sex were included as fixed and cohort was included as random effects in the model. Blood metabolites and cortisol were analyzed as repeated measures, and sampling day, pace × sampling day, and age × sampling day were also included as additional fixed effects. Significance was noted at P ≤ 0.05 and tendencies when 0.05 < P ≤ 0.10. The EA calves showed a tendency to have the greatest nonesterified fatty acid (NEFA) concentration compared with all other treatments. We observed a pace × day effect on serum NEFA and BHB; calves weaned at an abrupt pace had an increased level of NEFA after weaning compared with those weaned gradually. Calves weaned at the gradual pace showed the greatest serum BHB after weaning. Most mRNA abundances for inflammation-related genes affected by treatments showed a similar pattern. They were downregulated by the abrupt (liver IL-1β) and early weaning (jejunum TNF-α and ICAM), and in some cases, the interaction intensified the effect, demonstrating a weakened immune response in calves experiencing more stressful conditions (EA: IL-6 in the liver and NF-κB in the perirenal adipose tissue). Overall, the downregulation of the mRNA abundance of inflammation-related genes in EA calves may be attributed to the suppression of the immune system and an immature immune response. Furthermore, the greater NEFA in EA calves could be attributed to a reduced starter intake, less developed rumen, or shorter time during the weaning transition. [ABSTRACT FROM AUTHOR]

Summary: Maternal obesity is a well‐known risk factor for developing premature obesity, metabolic syndrome, cardiovascular disease and type 2 diabetes in the progeny. The development of white adipose tissue is a dynamic process that starts during prenatal life: fat depots laid down in utero are associated with the proportion of fat in children later on. How early this programming takes place is still unknown. However, recent evidence shows that mesenchymal stem cells (MSC), the embryonic adipocyte precursor cells, show signatures of the early setting of an adipogenic committed phenotype when exposed to maternal obesity. This review aims to present current findings on the cellular adaptations of MSCs from the offspring of women with obesity and how the metabolic environment of MSCs could affect the early commitment towards adipocytes. In conclusion, maternal obesity can induce early programming of fetal adipose tissue by conditioning MSCs. These cells have higher expression of adipogenic markers, altered insulin signalling and mitochondrial performance, compared to MSCs of neonates from lean pregnancies. Fetal MSCs imprinting by maternal obesity could help explain the increased risk of childhood obesity and development of further noncommunicable diseases. [ABSTRACT FROM AUTHOR]

Background: Plantar fasciitis is a painful tendinous condition (tendinopathy) with a high prevalence in athletes. While a healthy tendon has limited blood flow, ultrasound has indicated elevated blood flow in tendinopathy, but it is unknown if this is related to a de facto increase in the tendon vasculature. Likewise, an accumulation of glycosaminoglycans (GAGs) is observed in tendinopathy, but its relationship to clinical pain is unknown. Purpose: To explore to what extent vascularization, inflammation, and fat infiltration were present in patients with plantar fasciitis and if they were related to clinical symptoms. Study Design: Descriptive laboratory study. Methods: Biopsy specimens from tendinopathic plantar fascia tissue were obtained per-operatively from both the primary site of tendon pain and tissue swelling ("proximal") and a region that appeared macroscopically healthy at 1 to 2 cm away from the primary site ("distal") in 22 patients. Biopsy specimens were examined with immunofluorescence for markers of blood vessels, tissue cell density, fat infiltration, and macrophage level. In addition, pain during the first step in the morning (registered during an earlier study) was correlated with the content of collagen and GAGs in tissue. Results: High vascularization (and cellularity) was present in both the proximal (0.89%) and the distal (0.96%) plantar fascia samples, whereas inconsistent but not significantly different fat infiltration and macrophage levels were observed. The collagen content was similar in the 2 plantar fascia regions, whereas the GAG content was higher in the proximal region (3.2% in proximal and 2.8% in distal; P =.027). The GAG content in the proximal region was positively correlated with the subjective morning pain score in the patients with tendinopathy (n = 17). Conclusion: In patients with plantar fasciitis, marked tissue vascularization was present in both the painful focal region and a neighboring nonsymptomatic area. In contrast, the accumulation of hydrophilic GAGs was greater in the symptomatic region and was positively correlated with increased clinical pain levels in daily life. Clinical Relevance: The accumulation of GAGs in tissue rather than the extent of vascularization appears to be linked with the clinical degree of pain symptoms of the disease. [ABSTRACT FROM AUTHOR]

Declining estrogen (E2) leads to physical inactivity and adipose tissue (AT) dysfunction. Mechanisms are not fully understood, but E2's effects on dopamine (DA) activity in the nucleus accumbens (NAc) brain region may mediate changes in mood and voluntary physical activity (PA). Our prior work revealed that loss of E2 robustly affected NAc DA-related gene expression, and the pattern correlated with sedentary behavior and visceral fat. The current study used a new transgenic mouse model (D1ERKO) to determine whether the abolishment of E2 receptor alpha (ERα) signaling within DA-rich brain regions affects PA and AT metabolism. Adult male and female wild-type (WT) and D1ERKO (KD) mice were assessed for body composition, energy intake (EE), spontaneous PA (SPA), and energy expenditure (EE); underwent glucose tolerance testing; and were assessed for blood biochemistry. Perigonadal white AT (PGAT), brown AT (BAT), and NAc brain regions were assessed for genes and proteins associated with DA, E2 signaling, and metabolism; AT sections were also assessed for uncoupling protein (UCP1). KD mice had greater lean mass and EE (genotype effects) and a visible change in BAT phenotype characterized by increased UCP1 staining and lipid depletion, an effect seen only among females. Female KD had higher NAc Oprm1 transcript levels and greater PGAT UCP1. This group tended to have improved glucose tolerance (p = 0.07). NAc suppression of Esr1 does not appear to affect PA, yet it may directly affect metabolism. This work may lead to novel targets to improve metabolic dysfunction following E2 loss, possibly by targeting the NAc. [ABSTRACT FROM AUTHOR]

Patients with chronic hypoxia show a higher tumor incidence; however, no primary common cause has been recognized. Given the similarities between cellular reprogramming and oncogenic transformation, we directly compared these processes in human cells subjected to hypoxia. Mouse embryonic fibroblasts were employed as controls to compare transfection and reprogramming efficiency; human adipose-derived mesenchymal stem cells were employed as controls in human cells. Easily obtainable human peripheral blood mononuclear cells (PBMCs) were chosen to establish a standard protocol to compare cell reprogramming (into induced pluripotent stem cells (iPSCs)) and oncogenic focus formation efficiency. Cell reprogramming was achieved for all three cell types, generating actual pluripotent cells capable for differentiating into the three germ layers. The efficiencies of the cell reprogramming and oncogenic transformation were similar. Hypoxia slightly increased the reprogramming efficiency in all the cell types but with no statistical significance for PBMCs. Various PBMC types can respond to hypoxia differently; lymphocytes and monocytes were, therefore, reprogrammed separately, finding a significant difference between normoxia and hypoxia in monocytes in vitro. These differences were then searched for in vivo. The iPSCs and oncogenic foci were generated from healthy volunteers and patients with chronic obstructive pulmonary disease (COPD). Although higher iPSC generation efficiency in the patients with COPD was found for lymphocytes, this increase was not statistically significant for oncogenic foci. Remarkably, a higher statistically significant efficiency in COPD monocytes was demonstrated for both processes, suggesting that physiological hypoxia exerts an effect on cell reprogramming and oncogenic transformation in vivo in at least some cell types. [ABSTRACT FROM AUTHOR]

This study investigated the transcriptomic responses of subcutaneous adipose tissue (SAT) and liver in newborn Hanwoo calves subjected to maternal overnutrition during mid- to late gestation. Eight Hanwoo cows were randomly assigned to control and treatment groups. The treatment group received a diet of 4.5 kg of concentrate and 6.5 kg of rice straw daily, resulting in intake levels of 8.42 kg DMI, 5.69 kg TDN, and 0.93 kg CP—higher than the control group (6.07 kg DMI, 4.07 kg TDN, and 0.65 kg CP), with respective NEm values of 9.56 Mcal and 6.68 Mcal. Following birth, newly born calves were euthanized humanely as per ethical guidelines, and SAT and liver samples from newborn calves were collected for RNA extraction and analysis. RNA sequencing identified 192 genes that were differentially expressed in the SAT (17 downregulated and 175 upregulated); notably, HSPA6 emerged as the most significantly upregulated gene in the SAT and as the singular upregulated gene in the liver (adj-p value < 0.05). Additionally, differential gene expression analysis highlighted extensive changes across genes associated with adipogenesis, fibrogenesis, and stress response. The functional enrichment pathway and protein–protein interaction (PPI) unraveled the intricate networks and biological processes impacted by overnutrition, including extracellular matrix organization, cell surface receptor signaling, and the PI3K-Akt signaling pathway. These findings underscore maternal overnutrition's substantial influence on developmental pathways, suggesting profound cellular modifications with potential lasting effects on health and productivity. Despite the robust insights that are provided, the study's limitations (sample size) underscore the necessity for further research. [ABSTRACT FROM AUTHOR]

During the past half-century, although numerous interventions for obesity have arisen, the condition’s prevalence has relentlessly escalated annually. Obesity represents a substantial public health challenge, especially due to its robust correlation with co-morbidities, such as colorectal cancer (CRC), which often thrives in an inflammatory tumor milieu. Of note, individuals with obesity commonly present with calcium and vitamin D insufficiencies. Transient receptor potential canonical (TRPC) channels, a subclass within the broader TRP family, function as critical calcium transporters in calcium-mediated signaling pathways. However, the exact role of TRPC channels in both obesity and CRC pathogenesis remains poorly understood. This study set out to elucidate the part played by TRPC channels in obesity and CRC development using a mouse model lacking all seven TRPC proteins (TRPC HeptaKO mice). Relative to wildtype counterparts, TRPC HeptaKO mice manifested severe obesity, evidenced by significantly heightened body weights, augmented weights of epididymal white adipose tissue (eWAT) and inguinal white adipose tissue (iWAT), increased hepatic lipid deposition, and raised serum levels of total cholesterol (T-CHO) and lowdensity lipoprotein cholesterol (LDL-C). Moreover, TRPC deficiency was accompanied by an decrease in thermogenic molecules like PGC1-α and UCP1, alongside a upsurge in inflammatory factors within adipose tissue. Mechanistically, it was revealed that pro-inflammatory factors originating from inflammatory macrophages in adipose tissue triggered lipid accumulation and exacerbated obesity-related phenotypes. Intriguingly, considering the wellestablished connection between obesity and disrupted gut microbiota balance, substantial changes in the gut microbiota composition were detected in TRPC HeptaKO mice, contributing to CRC development. This study provides valuable insights into the role and underlying mechanisms of TRPC deficiency in obesity and its related complication, CRC. Our findings offer a theoretical foundation for the prevention of adverse effects associated with TRPC inhibitors, potentially leading to new therapeutic strategies for obesity and CRC prevention. [ABSTRACT FROM AUTHOR]

Menopause brings about profound physiological changes, including the acceleration of insulin resistance and other abnormalities, in which adipose tissue can play a significant role. This study analyzed the effect of ovariectomy and estradiol substitution on the metabolic parameters and transcriptomic profile of adipose tissue in prediabetic females of hereditary hypertriglyceridemic rats (HHTgs). The HHTgs underwent ovariectomy (OVX) or sham surgery (SHAM), and half of the OVX group received 17β-estradiol (OVX+E2) post-surgery. Ovariectomy resulted in weight gain, an impaired glucose tolerance, ectopic triglyceride (TG) deposition, and insulin resistance exemplified by impaired glycogenesis and lipogenesis. Estradiol alleviated some of the disorders associated with ovariectomy; in particular, it improved insulin sensitivity and reduced TG deposition. A transcriptomic analysis of perimetrial adipose tissue revealed 809 differentially expressed transcripts in the OVX vs. SHAM groups, mostly pertaining to the regulation of lipid and glucose metabolism, and oxidative stress. Estradiol substitution affected 1049 transcripts with overrepresentation in the signaling pathways of lipid metabolism. The principal component and hierarchical clustering analyses of transcriptome shifts corroborated the metabolic data, showing a closer resemblance between the OVX+E2 and SHAM groups compared to the OVX group. Changes in the adipose tissue transcriptome may contribute to metabolic abnormalities accompanying ovariectomy-induced menopause in HHTg females. Estradiol substitution may partially mitigate some of these disorders. [ABSTRACT FROM AUTHOR]

The editorial discusses the novel regulatory mechanisms behind the thermogenesis of brown and beige adipocytes, which play a crucial role in systemic metabolism by generating heat through non-shivering thermogenesis. The text explores the involvement of various regulators in the thermogenic transcriptional program, including factors like UCP1, norepinephrine, TRPM2, and GABPα. It also highlights the importance of alternative splicing, innovative experimental models like 3D cultures, and the inter-organ communication of thermogenic adipocytes. The research aims to understand these mechanisms to develop new therapeutic approaches against obesity and related metabolic disorders. [Extracted from the article]

The editorial in Frontiers in Endocrinology explores the roles of adipose tissue and adipokines in human reproduction, highlighting the complex relationship between adipose-derived hormones and reproductive functions. The research covers topics such as obesity's impact on female reproductive health, the association between adipokines and ovarian reserve in women, and the link between plasma lipid profiles and male infertility risk. The studies provide valuable insights into how adipose tissue and adipokines affect reproductive health and emphasize the need to integrate metabolic and hormonal factors into research on reproductive disorders. [Extracted from the article]

Proposed as a non-invasive alternative to address a variety of patient concerns including cellulite, body sculpting, weight reduction and skin rejuvenation, mesotherapy remains a controversial therapy, with some arguing that it is ineffective at best and potentially dangerous at worst. However, other practitioners and researchers swear by its efficacy. Francesca Ramadan dives into the current evidence base, safety profile and applications of mesotherapy. [ABSTRACT FROM AUTHOR]

This document is an editorial published in the journal Frontiers in Endocrinology. It discusses the importance of communication between metabolic organs, such as adipose tissues and the heart, in modulating energy homeostasis and metabolism. The editorial highlights the role of factors secreted by these organs, including peptides, metabolites, lipids, and microRNAs, in establishing communication with other cell types and organs. The goal of the research topic presented in the editorial is to investigate how this communication may impact the onset and progression of metabolic syndromes such as obesity, diabetes, metabolic dysfunction-associated steatotic liver disease, and cardiovascular diseases. The research topic includes four original articles, three reviews, and one study protocol that explore various aspects of this crosstalk between metabolic organs. [Extracted from the article]

The article discusses the potential of adipose tissue-derived stem cells (ADSCs) in regenerative medicine, focusing on their therapeutic benefits in tissue regeneration and disease treatment. ADSCs have shown promising results in clinical trials, particularly in inflammatory conditions like psoriasis, due to their immunoregulatory and anti-inflammatory properties. The article emphasizes the importance of dosing stem cells for therapy to maximize beneficial effects and highlights ongoing research on ADSCs' potential in various medical applications. [Extracted from the article]

Background: Diabetes in pregnancy is associated with increased risk of long-term metabolic disease in the offspring, potentially mediated by in utero epigenetic variation. Previously, we identified multiple differentially methylated single CpG sites in offspring of women with gestational diabetes mellitus (GDM), but whether stretches of differentially methylated regions (DMRs) can also be identified in adolescent GDM offspring is unknown. Here, we investigate which DNA regions in adolescent offspring are differentially methylated in blood by exposure to diabetes in pregnancy. The secondary aim was to characterize the RNA expression of the identified DMR, which contained the nc886 non-coding RNA. Methods: To identify DMRs, we employed the bump hunter method in samples from young (9–16 yr, n = 92) offspring of women with GDM (O-GDM) and control offspring (n = 94). Validation by pyrosequencing was performed in an adult offspring cohort (age 28–33 years) consisting of O-GDM (n = 82), offspring exposed to maternal type 1 diabetes (O-T1D, n = 67) and control offspring (O-BP, n = 57). RNA-expression was measured using RT-qPCR in subcutaneous adipose tissue and skeletal muscle. Results: One significant DMR represented by 10 CpGs with a bimodal methylation pattern was identified, located in the nc886/VTRNA2-1 non-coding RNA gene. Low methylation status across all CpGs of the nc886 in the young offspring was associated with maternal GDM. While low methylation degree in adult offspring in blood, adipose tissue, and skeletal muscle was not associated with maternal GDM, adipose tissue nc886 expression was increased in O-GDM compared to O-BP, but not in O-T1D. In addition, adipose tissue nc886 expression levels were positively associated with maternal pre-pregnancy BMI (p = 0.006), but not with the offspring's own adiposity. Conclusions: Our results highlight that nc886 is a metastable epiallele, whose methylation in young offspring is negatively correlated with maternal obesity and GDM status. The physiological effect of nc886 may be more important in adipose tissue than in skeletal muscle. Further research should aim to investigate how nc886 regulation in adipose tissue by exposure to GDM may contribute to development of metabolic disease. [ABSTRACT FROM AUTHOR]

Deciphering lipid metabolism in white adipose tissue (WAT) depots during weight gain is important to understand the heterogeneity of WAT and its roles in obesity. Here, we examined the expression of key enzymes of lipid metabolism and changes in the morphology of representative visceral (epididymal) and subcutaneous (inguinal) WAT (eWAT and iWAT, respectively)-in adult male rats acclimated to cold (4 ± 1 °C) for 45 days and reacclimated to room temperature (RT, 22 ± 1 °C) for 1, 3, 7, 12, 21, or 45 days. The relative mass of both depots decreased to a similar extent after cold acclimation. However, fatty acid synthase (FAS), glucose-6-phosphate dehydrogenase (G6PDH), and medium-chain acyl-CoA dehydrogenase (ACADM) protein level increased only in eWAT, whereas adipose triglyceride lipase (ATGL) expression increased only in iWAT. During reacclimation, the relative mass of eWAT reached control values on day 12 and that of iWAT on day 45 of reacclimation. The faster recovery of eWAT mass is associated with higher expression of FAS, acetyl-CoA carboxylase (ACC), G6PDH, and ACADM during reacclimation and a delayed increase in ATGL. The absence of an increase in proliferating cell nuclear antigen suggests that the observed depot-specific mass increase is predominantly due to metabolic adjustments. In summary, this study shows a differential rate of visceral and subcutaneous adipose tissue weight regain during post-cold reacclimation of rats at RT. Faster recovery of the visceral WAT as compared to subcutaneous WAT during reacclimation at RT could be attributed to observed differences in the expression patterns of lipid metabolic enzymes. [ABSTRACT FROM AUTHOR]

Obesity and its related metabolic complications represent a significant global health challenge. Central to this is the dysregulation of glucolipid metabolism, with a predominant focus on glucose metabolic dysfunction in the current research, whereas adipose metabolism impairment garners less attention. Exosomes (EXs), small extracellular vesicles (EVs) secreted by various cells, have emerged as important mediators of intercellular communication and have the potential to be biomarkers, targets, and therapeutic tools for diverse diseases. In particular, EXs have been found to play a role in adipose metabolism by transporting cargoes such as noncoding RNAs (ncRNA), proteins, and other factors. This review article summarizes the current understanding of the role of EXs in mediating adipose metabolism disorders in obesity. It highlights their roles in adipogenesis (encompassing adipogenic differentiation and lipid synthesis), lipid catabolism, lipid transport, and white adipose browning. The insights provided by this review offer new avenues for developing exosome-based therapies to treat obesity and its associated comorbidities. [ABSTRACT FROM AUTHOR]

Aims: Inflammation is central to the pathogenesis of metabolic syndrome (MetS). Leukocyte cell-derived chemotaxin 2 (LECT2) is constitutively secreted in response to inflammatory stimuli and oxidative stress contributing to tissue or systemic inflammation. We explored the relationship between LECT2 levels and MetS severity in humans and mice. Methods: Serum LECT2 levels were measured in 210 participants with MetS and 114 without MetS (non-MetS). LECT2 expression in the liver and adipose tissue was also examined in mice fed a high-fat diet (HFD) and genetically obese (ob/ob) mice. Results: Serum LECT2 levels were significantly higher in MetS participants than in non-MetS participants (7.47[3.36–17.14] vs. 3.74[2.61–5.82], P < 0.001). Particularly, serum LECT2 levels were significantly elevated in participants with hypertension, central obesity, diabetes mellitus (DM), hyperglycaemia, elevated triglyceride (TG) levels, and reduced high-density lipoprotein cholesterol (HDL-C) levels compared to those in participants without these conditions. Pearson's correlation analysis showed that serum LECT2 levels were positively associated with conventional risk factors in all patients. Moreover, LECT2 was positively associated with the number of MetS components (r = 0.355, P < 0.001), indicating that higher serum LECT2 levels reflected MetS severity. Multivariate regression analysis revealed that a one standard deviation increase in LECT2 was associated with an odds ratio of 1.52 (1.01–2.29, P = 0.044) for MetS prevalence after adjusting for age, sex, body mass index, waist circumference, smoking status, white blood cell count, fasting blood glucose, TG, total cholesterol, HDL-C, blood urea nitrogen, and alanine aminotransferase. Receiver operating characteristic curve analysis confirmed the strong predictive ability of serum LECT2 levels for MetS. The optimum serum LECT2 cut-off value was 9.05. The area under the curve was 0.73 (95% confidence interval 0.68–0.78, P < 0.001), with a sensitivity and specificity of 45.71% and 95.61%, respectively. Additionally, LECT2 expression levels were higher at baseline and dramatically enhanced in metabolic organs (e.g. the liver) and adipose tissue in HFD-induced obese mice and ob/ob mice. Conclusions: Increased LECT2 levels were significantly and independently associated with the presence and severity of MetS, indicating that LECT2 could be used as a novel biomarker and clinical predictor of MetS. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the effects of a new treatment—conditioned medium from human orbital adipose-derived stem cells (OASC-CM)—on corneal recovery after alkali burns in a rabbit model. Methods: The corneal alkali burn rabbit model was established and treated with OASC-CM, conditioned medium from human abdominal subcutaneous adipose-derived stem cells (ABASC-CM), and fresh control culture medium (con-CM) three times a day for 7 days, respectively. Subsequently, the treatment effects were evaluated and compared through clinical, histological, immunohistochemical, and cytokine evaluations. Results: Clinically, OASC-CM alleviated corneal opacity and edema and promoted recovery of corneal epithelium defect. Histologically and immunohistochemically, OASC-CM inhibited neovascularization, conjunctivalization, and immuno-inflammatory reaction, while promoting corneal regeneration and rearrangement. Increased secretion of interleukin-10 and inhibited protein levels of cluster of differentiation 45, interferon-γ, and tumor necrosis factor-α were observed in the alkali-burned cornea after OASC-CM treatment, which might be the relevant molecular mechanism. Conclusions: OASC-CM showed significant effects on the recovery of rabbit corneal alkali burns and eliminated immunological and ethical limitations, representing a new option for corneal wound treatment. [ABSTRACT FROM AUTHOR]

Obesity is often accompanied by increased adipose tissue inflammation, a process that is partially driven by adipose tissue-resident macrophages. In this study, we explored the potential for plant-derived dietary compounds to exert anti-inflammatory effects in macrophages that alleviate obesity-associated adipocyte dysfunction. Capsaicin (CAP), schisandrin A (SA), enterodiol (END), and enterolactone (ENL) treatment polarized J774 macrophages to an “M2” or anti-inflammatory phenotype and inhibited responses to stimulation with lipopolysaccharide (LPS). Furthermore, these compounds blocked inflammasome activation when administered just before ATP-induced NLRP3 activation, as evidenced by the abrogation of IL-1β release in mouse macrophages and human peripheral blood monocytes. The addition of CAP, SA, or ENL during the differentiation of bone marrow-derived macrophages was also sufficient to inhibit LPS-induced IL-6 and TNFα production. Finally, CAP, END, and ENL treatment during differentiation of 3T3-L1 adipocytes induced an adiponectin-high phenotype accompanied by increases in thermogenic gene expression, and conditioned media from these adipocytes inhibited LPS-induced production of IL-1β, IL-6, and TNFα from J774 macrophages. These polarizing effects were partially mediated by the elevated adiponectin and decreased syndecan-4 in the adipocyte-conditioned media. These results implicate the contribution of plant-derived dietary components to the modulation of macrophages and adipocytes in obesity.NEW & NOTEWORTHY The utility of food-based products to prevent or alleviate chronic conditions such as obesity and its associated comorbidities is an attractive approach. Capsaicin, schisandrin A, enterodiol, and enterolactone, phytochemicals present in traditional medicinal food, decreased proinflammatory cytokine production from macrophages that, in turn, reduced obesity-associated adipocyte dysfunction. These results implicate the contribution of plant-derived dietary components to the modulation of macrophages and adipocytes in obesity. [ABSTRACT FROM AUTHOR]

In the past few decades, genomic selection and other refined strategies have been used to increase the growth rate and lean meat production of beef cattle. Nevertheless, the fast growth rates of cattle breeds are often accompanied by a reduction in intramuscular fat (IMF) deposition, impairing meat quality. Transcription factors play vital roles in regulating adipogenesis and lipogenesis in beef cattle. Meanwhile, understanding the role of transcription factors in regulating adipogenesis and lipogenesis in beef cattle has gained significant attention to increase IMF deposition and meat quality. Therefore, the aim of this paper was to provide a comprehensive summary and valuable insight into the complex role of transcription factors in adipogenesis and lipogenesis in beef cattle. This review summarizes the contemporary studies in transcription factors in adipogenesis and lipogenesis, genome‐wide analysis of transcription factors, epigenetic regulation of transcription factors, nutritional regulation of transcription factors, metabolic signalling pathways, functional genomics methods, transcriptomic profiling of adipose tissues, transcription factors and meat quality and comparative genomics with other livestock species. In conclusion, transcription factors play a crucial role in promoting adipocyte development and fatty acid biosynthesis in beef cattle. They control adipose tissue formation and metabolism, thereby improving meat quality and maintaining metabolic balance. Understanding the processes by which these transcription factors regulate adipose tissue deposition and lipid metabolism will simplify the development of marbling or IMF composition in beef cattle. [ABSTRACT FROM AUTHOR]

Objective: To determine the correlation between visceral adipose tissue (VAT) and degree of coronary artery stenosis in the Thai population. Materials and Methods: This prospective cross-sectional study was conducted in 220 Thai postmortem cases. Sex, age, weight, height, waist and hip circumferences were recorded for each case. The intra-abdominal VAT weight of each site was assessed during the autopsy procedure, and degrees of stenosis for three coronary arteries (left anterior descending artery (LAD), right coronary artery (RCA) and left circumflex artery (LCX)) were evaluated in histological examination. Descriptive statistics, bivariate correlation, and multivariate linear regression were used to determine the correlations between VAT and degrees of coronary artery stenosis. Results: There were 108 female and 112 male subjects with a mean age of 45.95 years old. Waist circumference, waist-hip ratio and VAT in the male subjects were significantly higher than in the female subjects (p<0.001). VAT was well correlated with waist circumference and waist-hip ratio (p<0.001). VAT weights were positively correlated with degrees of LAD, RCA and LCX stenosis, with coefficient correlations (r) of 0.561, 0.453 and 0.451, respectively (p<0.001). Mesenteric and peri-renal adipose tissues produced better correlations than the other sites. Multivariate linear regression showed that sex and age were correlated with stenosis in all three coronary arteries (p<0.001), and mesenteric and peri-renal adipose tissues had strong correlations with LAD stenosis (p<0.001). Conclusion: VAT weights from all sites were correlated with degrees of coronary artery stenosis. Mesenteric and peri-renal adipose tissues produced better correlations than the other sites. [ABSTRACT FROM AUTHOR]

Ketosis, especially its subclinical form, is frequently observed in high-yielding dairy cows and is linked to various diseases during the transition period. Although adipose tissue plays a significant role in the development of metabolic disorders, its exact impact on the emergence of subclinical ketosis (SCK) is still poorly understood. The objectives of this study were to characterize and compare the profiling of transcriptome and lipidome of blood and adipose tissue between SCK and healthy cows and investigate the potential correlation between metabolic disorders and lipid metabolism. We obtained blood and adipose tissue samples from healthy cows (CON, n = 8, β-hydroxybutyric acid concentration < 1.2 mmol/L) and subclinical ketotic cows (SCK, n = 8, β-hydroxybutyric acid concentration = 1.2–3.0 mmol/L) for analyzing biochemical parameters, transcriptome, and lipidome. We found that serum levels of nonesterified fatty acids, malonaldehyde, serum amyloid A protein, IL-1β, and IL-6 were higher in SCK cows than in CON cows. Levels of adiponectin and total antioxidant capacity were higher in serum and adipose tissue from SCK cows than in CON cows. The top enriched pathways in whole blood and adipose tissue were associated with immune and inflammatory responses and sphingolipid metabolism, respectively. The accumulation of ceramide and sphingomyelin in adipose tissue was paralleled by an increase in genes related to ceramide biosynthesis, lipolysis, and inflammation and a decrease in genes related to ceramide catabolism, lipogenesis, adiponectin production, and antioxidant enzyme systems. Increased ceramide concentrations in blood and adipose tissue correlated with reduced insulin sensitivity. The current results indicate that the lipid profile of blood and adipose tissue is altered with SCK and that certain ceramide species correlate with metabolic health. Our research suggests that disruptions in ceramide metabolism could be crucial in the progression of SCK, exacerbating conditions such as insulin resistance, increased lipolysis, inflammation, and oxidative stress, providing a potential biomarker of SCK and a novel target for nutritional manipulation and pharmacological therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Chicken adipose tissue is essential in maintaining energy homeostasis and is also associated with the development of fatty liver. The liver and adipose tissue cooperatively promote energy balance, metabolic stability, and hormonal regulation in the body. This study investigated the effects of a high-energy low-protein (HELP) diet on laying hens as well as explored the dynamic changes in metabolism and inflammation in the liver and abdominal adipose tissue (AAT). The results showed that lipid peroxidation and inflammatory responses occur simultaneously in the liver and AATs of laying hens fed a HELP diet. This suggests a potential reciprocal regulation between the liver and AAT during the development of fatty liver in laying hens. The aim of this study was to evaluate the effects of a high-energy low-protein (HELP) diet on lipid metabolism and inflammation in the liver and abdominal adipose tissue (AAT) of laying hens. A total of 200 Roman laying hens (120 days old) were randomly divided into two experimental groups: negative control group (NC group) and HELP group, with 100 hens per group. The chickens in the NC group were fed with a basic diet, whereas those in the HELP group were given a HELP diet. Blood, liver, and AAT samples were collected from 20 chickens per group at each experimental time point (30, 60, and 90 d). The morphological and histological changes in the liver and AAT were observed, and the level of serum biochemical indicators and the relative expression abundance of key related genes were determined. The results showed that on day 90, the chickens in the HELP group developed hepatic steatosis and inflammation. However, the diameter of the adipocytes of AAT in the HELP group was significantly larger than that of the NC group. Furthermore, the results showed that the extension of the feeding time significantly increased the lipid contents, lipid deposition, inflammatory parameters, and peroxide levels in the HELP group compared with the NC group, whereas the antioxidant parameters decreased significantly. The mRNA expression levels of genes related to lipid synthesis such as fatty acid synthase (FASN), stearoyl-coA desaturase (SCD), fatty acid binding protein 4 (FABP4), and peroxisome proliferator-activated receptor gamma (PPARγ) increased significantly in the liver and AAT of the HELP group, whereas genes related to lipid catabolism decreased significantly in the liver. In addition, the expression of genes related to lipid transport and adipokine synthesis decreased significantly in the AAT, whereas in the HELP group, the expression levels of pro-inflammatory parameters such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) increased significantly in the liver and AAT. Conversely, the expression level of the anti-inflammatory parameter interleukin-10 (IL-10) decreased significantly in the liver. The results indicated that the HELP diet induced lipid peroxidation and inflammation in the liver and AAT of the laying hens. Hence, these results suggest that chicken AAT may be involved in the development of fatty liver. [ABSTRACT FROM AUTHOR]

During the periparturient period, dairy cows exhibit negative energy balance due to limited appetite and increased energy requirements for lactogenesis. The delicate equilibrium between energy availability and expenditure puts cows in a state of metabolic stress characterized by excessive lipolysis in white adipose tissues (AT), increased production of reactive oxygen species, and immune cell dysfunction. Metabolic stress, especially in AT, increases the risk for metabolic and inflammatory diseases. Around parturition, cows are also susceptible to endotoxemia. Bacterial-derived toxins cause endotoxemia by promoting inflammatory processes and immune cell infiltration in different organs and systems while impacting metabolic function by altering lipolysis, mitochondrial activity, and insulin sensitivity. In dairy cows, endotoxins enter the bloodstream after overcoming the defense mechanisms of the epithelial barriers, particularly during common periparturient conditions such as mastitis, metritis, and pneumonia, or after abrupt changes in the gut microbiome. In the bovine AT, endotoxins induce a pro-inflammatory response and stimulate lipolysis in AT, leading to the release of free fatty acids into the bloodstream. When excessive and protracted, endotoxin-induced lipolysis can impair adipocyte's insulin signaling pathways and lipid synthesis. Endotoxin exposure can also induce oxidative stress in AT through the production of reactive oxygen species by inflammatory cells and other cellular components. This review provides insights into endotoxins' impact on AT function, highlighting the gaps in our knowledge of the mechanisms underlying AT dysfunction, its connection with periparturient cows' disease risk, and the need to develop effective interventions to prevent and treat endotoxemia-related inflammatory conditions in dairy cattle. [ABSTRACT FROM AUTHOR]

Individuals who are overweight or obese are at increased risk of developing prediabetes and type 2 diabetes, yet the direct molecular mechanisms that connect diabetes to obesity are not clear. Chronic, sustained inflammation is considered a strong risk factor in these interactions, directed in part by the short-lived gene expression programs encoding for cytokines and pro-inflammatory mediators. In this study, we show that triptolide administration in the C57BL/6 diet-induced obese mice at up to 10 μg/kg/day for 10 weeks attenuated the development of insulin resistance and diabetes, but not obesity, in these animals. Significant reductions in adipose tissue inflammation and improved insulin sensitivity were observed in the absence of changes in food intake, body weight, body composition, or energy expenditure. Analysis of the core cluster of biomarkers that drives pro-inflammatory responses in the metabolic tissues suggested TNF-α as a critical point that affected the co-development of inflammation and insulin resistance, but also pointed to the putatively protective roles of increased COX-2 and IL-17A signaling in the mediation of these pathophysiological states. Our results show that reduction of diet-induced inflammation confers partial protection against insulin resistance, but not obesity, and suggest the possibility of achieving overweight phenotypes that are accompanied by minimal insulin resistance if inflammation is controlled. [ABSTRACT FROM AUTHOR]

(1) Background: Systemic inflammation stands as a well-established risk factor for ischemic cardiovascular disease, as well as a contributing factor in the development of cardiac arrhythmias, notably atrial fibrillation. Furthermore, scientific studies have brought to light the pivotal role of localized vascular inflammation in the initiation, progression, and destabilization of coronary atherosclerotic disease. (2) Methods: We comprehensively review recent, yet robust, scientific evidence elucidating the use of perivascular adipose tissue attenuation measurement on computed tomography applied to key anatomical sites. Specifically, the investigation extends to the internal carotid artery, aorta, left atrium, and coronary arteries. (3) Conclusions: The examination of perivascular adipose tissue attenuation emerges as a non-invasive and indirect means of estimating localized perivascular inflammation. This measure is quantified in Hounsfield units, indicative of the inflammatory response elicited by dense adipose tissue near the vessel or the atrium. Particularly noteworthy is its potential utility in assessing inflammatory processes within the coronary arteries, evaluating coronary microvascular dysfunction, appraising conditions within the aorta and carotid arteries, and discerning inflammatory states within the atria, especially in patients with atrial fibrillation. The widespread applicability of perivascular adipose tissue attenuation measurement underscores its significance as a diagnostic tool with considerable potential for enhancing our understanding and management of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) is a clinical condition associated with multiple metabolic risk factors leading to type 2 diabetes mellitus and other metabolic diseases. Recent evidence suggests that modulating adipose tissue to adaptive thermogenesis may offer therapeutic potential for MetS. Xiasangju (XSJ) is a marketed drug and dietary supplement used for the treatment of metabolic disease with anti-inflammatory activity. This study investigated the therapeutic effects of XSJ and the underlying mechanisms affecting the activation of brown adipose tissue (BAT) in MetS. The results revealed that XSJ ameliorated MetS by enhancing glucose and lipid metabolism, leading to reduced body weight and abdominal circumference, decreased adipose tissue and liver index, and improved blood glucose tolerance. XSJ administration stimulated catecholamine biosynthesis, increasing noradrenaline (NA) levels and activating NA-mediated proteins in BAT. Thus, BAT enhanced thermogenesis and oxidative phosphorylation (OXPHOS). Moreover, XSJ induced changes in gut microbiota composition, with an increase in Oscillibacter abundance and a decrease in Bilophila, Candidatus Stoquefichus, Holdemania, Parasutterella and Rothia. XSJ upregulated the proteins associated with intestinal tight junctions corresponding with lower serum lipopolysaccharide (LPS), tumor necrosis factor α (TNF-α) monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) levels to maintain NA signaling transport. In summary, XSJ may alleviate MetS by promoting thermogenesis in BAT to ultimately boost energy metabolism through increasing NA biosynthesis, strengthening intestinal barrier integrity and reducing low-grade inflammation. These findings suggest XSJ has potential as a natural therapeutic agent for the treatment of MetS. [ABSTRACT FROM AUTHOR]

Intrathecal delivery of autologous culture-expanded adipose tissue-derived mesenchymal stem cells (AD-MSC) could be utilized to treat traumatic spinal cord injury (SCI). This Phase I trial (ClinicalTrials.gov: NCT03308565) included 10 patients with American Spinal Injury Association Impairment Scale (AIS) grade A or B at the time of injury. The study's primary outcome was the safety profile, as captured by the nature and frequency of adverse events. Secondary outcomes included changes in sensory and motor scores, imaging, cerebrospinal fluid markers, and somatosensory evoked potentials. The manufacturing and delivery of the regimen were successful for all patients. The most commonly reported adverse events were headache and musculoskeletal pain, observed in 8 patients. No serious AEs were observed. At final follow-up, seven patients demonstrated improvement in AIS grade from the time of injection. In conclusion, the study met the primary endpoint, demonstrating that AD-MSC harvesting and administration were well-tolerated in patients with traumatic SCI. In the CELLTOP Phase I trial, stem cells were harvested from patients with spinal cord injury and injected into their central nervous system after processing. The procedure was safe, with no reported serious adverse events during the 2-year follow-up period. [ABSTRACT FROM AUTHOR]

Aim: One of the most critical functions of adipose tissue is the production of adipokines, ie, numerous active substances that regulate metabolism. One is the newly discovered FAM19A5, whose older name is TAFA-5. Purpose: The study aimed to review the literature on the FAM19A5 protein. Methods: The review was conducted in December 2023 using the PubMed (Medline) search engine. Sixty-four papers were included in the review. Results: This protein exhibits the characteristics of an adipokine with positive features for maintaining homeostasis. The results showed that FAM19A5 was highly expressed in adipose tissue, with mild to moderate expression in the brain and ovary. FAM19A5 may also inhibit vascular smooth muscle cell proliferation and migration through the perivascular adipose tissue paracrine pathway. Serum levels of FAM19A5 were decreased in obese children compared with healthy controls. There are negative correlations between FAM19A5, body mass index, and fasting insulin. Serum FAM19A5 level is correlated with type 2 diabetes, waist circumference, waist-to-hip ratio, glutamic pyruvic transferase, fasting plasma glucose, HbA1c, and mean shoulder pulse wave velocity. FAM19A5 expression was reduced in mice with obesity. However, the data available needs to be clarified or contradictory. Conclusion: Considering today's knowledge about FAM19A5, we cannot consider this protein as a biomarker of the metabolic syndrome. According to current knowledge, FAM19A5 cannot be considered a marker of metabolic disorders because the results of studies conducted in this area are unclear. [ABSTRACT FROM AUTHOR]