Brown Adipose Tissue Research Articles

Biodistribution and Biotoxicity Assessment of Fluorescent Conjugated Polymer Dots.

Conjugated polymer dots (Pdots) have shown potential in the biomedical fields due to their optical properties and customizable design. However, the limited research on the biotoxicity of Pdots hinders their further application and translation. Lipophilic Pdots are prone to adsorbing specific proteins, leading to targeted tissue accumulation. Therefore, lipophilic fluorescent Pdots (Bare-Pdots) are synthesized using the conjugated polymer poly[2-methoxy-5-(2'-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV) to systematically evaluate their biodistribution and biotoxicity in stem cells, zebrafish embryos, and mice. It is observed that Bare-Pdots are readily internalized by cells and adhered to the embryonic chorion. Additionally, Bare-Pdots exhibit a distinct distribution in brown adipose tissue and heart, closely associated with phagocytosis of capillary endothelial cells involved in lipid metabolism. Notably, injection of Bare-Pdots at 5mgkg-1results in dysfunction of brown adipose tissue and an increased risk of obesity 90days post-injection. Furthermore, hydrophilic COOH-Pdots and NH2-Pdots with reduced lipophilicity are synthesized using amphiphilic ligands. NH2-Pdots show similar distribution but lower biotoxicity compared to Bare-Pdots. Nevertheless, injection of COOH-Pdots at 5mgkg-1 causes a decrease in white blood cells and renal tubular damage. These findings provide valuable insights for optimizing dosage to ensure the safe use of Pdots in preclinical applications.

Correction of Nathan Vidal et al. (2023). Assessing the reliability of an infrared thermography protocol to assess cold-induced brown adipose tissue activation in French psychology students

Correction of Nathan Vidal et al. (2023). Assessing the reliability of an infrared thermography protocol to assess cold-induced brown adipose tissue activation in French psychology students

Gene expression and characterization of clonally derived murine embryonic brown and brite adipocytes.

White adipocytes store energy, while brown and brite adipocytes release heat via nonshivering thermogenesis. In this study, we characterized two murine embryonic clonal preadipocyte lines, EB5 and EB7, each displaying unique gene marker expression profiles. EB5 cells differentiate into brown adipocytes, whereas EB7 cells into brite (also known as beige) adipocytes. To draw a comprehensive comparison, we contrasted the gene expression patterns, adipogenic capacity, as well as carbohydrate and lipid metabolism of these cells to that of F442A, a well-known white preadipocyte and adipocyte model. We found that commitment to differentiation in both EB5 and EB7 cells can be induced by 3-Isobutyl-1-methylxanthine/dexamethasone (Mix/Dex) and staurosporine/dexamethasone (St/Dex) treatments. Additionally, the administration of rosiglitazone significantly enhances the brown and brite adipocyte phenotypes. Our data also reveal the involvement of a series of genes in the transcriptional cascade guiding adipogenesis, pinpointing GSK3β as a critical regulator for both EB5 and EB7 adipogenesis. In a developmental context, we observe that, akin to brown fat progenitors, brite fat progenitors make their appearance in murine development by 11-12 days of gestation or potentially earlier. This result contributes to our understanding of adipocyte lineage specification during embryonic development. In conclusion, EB5 and EB7 cell lines are valuable for research into adipocyte biology, providing insights into the differentiation and development of brown and beige adipocytes. Furthermore, they could be useful for the characterization of drugs targeting energy balance for the treatment of obesity and metabolic diseases.

Effects of KGM and Degradation Products on Appetite Regulation and Energy Expenditure in High-Fat-Diet Mice via the Adipocyte-Hypothalamus Axis.

Konjac glucomannan (KGM), high-viscosity dietary fiber, is utilized in weight management. Previous investigations on the appetite-suppressing effects of KGM have centered on intestinal responses to nutrients and gastric emptying rates, with less focus on downstream hypothalamic neurons of satiety hormones. In our studies, the molecular mechanisms through which KGM and its degradation products influence energy homeostasis via the adipocyte-hypothalamic axis have been examined. It was found that high-viscosity KGM more effectively stimulates enteroendocrine cells to release glucagon-like peptide-1 (GLP-1) and reduces ghrelin production, thereby activating hypothalamic neurons and moderating short-term satiety. Conversely, low-viscosity DKGM has been shown to exhibit stronger anti-inflammatory properties in the hypothalamus, enhancing hormone sensitivity and lowering the satiety threshold. Notably, both KGM and DKGM significantly reduced leptin signaling and fatty acid signaling in adipose tissue and activated brown adipose tissue thermogenesis to suppress pro-opiomelanocortin (POMC) expression and activate agouti-related protein (AgRP) expression, thereby reducing food intake and increasing energy expenditure. Additionally, high-viscosity KGM has been found to activate the adipocyte-hypothalamus axis more effectively than DKGM, thereby promoting greater daily energy expenditure. These findings provide novel insights into the adipocyte-hypothalamic axis for KGM to suppress appetite and reduce weight.

Thermogenic Fat as a New Obesity Management Tool: From Pharmaceutical Reagents to Cell Therapies.

Obesity is a complex medical condition caused by a positive imbalance between calorie intake and calorie consumption. Brown adipose tissue (BAT), along with the newly discovered "brown-like" adipocytes (called beige cells), functions as a promising therapeutic tool to ameliorate obesity and metabolic disorders by burning out extra nutrients in the form of heat. Many studies in animal models and humans have proved the feasibility of this concept. In this review, we aim to summarize the endeavors over the last decade to achieve a higher number/activity of these heat-generating adipocytes. In particular, pharmacological compounds, especially agonists to the β3 adrenergic receptor (β3-AR), are reviewed in terms of their feasibility and efficacy in elevating BAT function and improving metabolic parameters in human subjects. Alternatively, allograft transplantation of BAT and the transplantation of functional brown or beige adipocytes from mesenchymal stromal cells or human induced pluripotent stem cells (hiPSCs) make it possible to increase the number of these beneficial adipocytes in patients. However, practical and ethical issues still need to be considered before the therapy can eventually be applied in the clinical setting. This review provides insights and guidance on brown- and beige-cell-based strategies for the management of obesity and its associated metabolic comorbidities.

The metabolic benefits of thermogenic stimulation are preserved in aging.

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 US (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. Our study provides foundational evidence for targeting adipose thermogenesis to improve age-related metabolic dysfunction.

IGF-1 Acts through Kiss1-expressing Cells to Influence Metabolism and Reproduction.

Kisspeptin, encoded by the Kiss1 gene, ties puberty and fertility to energy status; however, the metabolic factors that control Kiss1-expressing cells need to be clarified. To evaluate the impact of IGF-1 on the metabolic and reproductive functions of kisspeptin producing cells, we created mice with IGF-1 receptor deletion driven by the Kiss1 promoter (IGF1RKiss1 mice). Previous studies have shown IGF-1 and insulin can bind to each other's receptor, permitting IGF-1 signaling in the absence of IGF1R. Therefore, we also generated mice with simultaneous deletion of the IGF1R and insulin receptor (IR) in Kiss1-expressing cells (IGF1R/IRKiss1 mice). Loss of IGF1R in Kiss1 cells caused stunted body length. In addition, female IGF1RKiss1 mice displayed lower body weight and food intake plus higher energy expenditure and physical activity. This phenotype was linked to higher proopiomelanocortin (POMC) expression and heightened brown adipose tissue (BAT) thermogenesis. Male IGF1RKiss1 mice had mild changes in metabolic functions. Moreover, IGF1RKiss1 mice of both sexes experienced delayed puberty. Notably, male IGF1RKiss1 mice had impaired adulthood fertility accompanied by lower gonadotropin and testosterone levels. Thus, IGF1R in Kiss1-expressing cells impacts metabolism and reproduction in a sex-specific manner. IGF1R/IRKiss1 mice had higher fat mass and glucose intolerance, suggesting IGF1R and IR in Kiss1-expressing cells together regulate body composition and glucose homeostasis. Overall, our study shows that IGF1R and IR in Kiss1 have cooperative roles in body length, metabolism, and reproduction.

Comparative analysis of two independent Myh6-Cre transgenic mouse lines

We have previously shown that the Myh6 promoter drives Cre expression in a subset of male germ line cells in three independent Myh6-Cre mouse lines, including two transgenic lines and one knock-in allele. In this study, we further compared the tissue-specificity of the two Myh6-Cre transgenic mouse lines, MDS Myh6-Cre and AUTR Myh6-Cre, through examining the expression of tdTomato (tdTom) red fluorescence protein in multiple internal organs, including the heart, brain, liver, lung, pancreas and brown adipose tissue. Our results show that MDS Myh6-Cre mainly activates tdTom reporter in the heart, whereas AUTR Myh6-Cre activates tdTom expression significantly in the heart, and in the cells of liver, pancreas and brain. In the heart, similar to MDS Myh6-Cre,AUTR Myh6-Cre activates tdTom in most cardiomyocytes. In the other organs, AUTR Myh6-Cre not only mosaically activates tdTom in some parenchymal cells, such as hepatocytes in the liver and neurons in the brain, but also turns on tdTom in some interstitial cells of unknown identity.

Atomically precise gold nanoclusters as ROS-scavenging clusterzymes to treat high-fat diet-induced obesity

Obesity is widely considered a chronic inflammatory disease and is recognized as one of the major challenges to global public health, but there is no successful anti-inflammatory therapy for obesity so far. In this study, atomically precise Au22 nanoclusters are introduced as reactive oxygen species (ROS)-scavenging clusterzymes, with the aim of achieving anti-inflammation in high-fat diet (HFD)-induced obesity. Au22 clusterzymes display high catalase (CAT)-like and superoxide dismutase (SOD)-like activities, excellent antioxidant capacity. We demonstrate that Au22 clusterzymes treatment can effectively scavenge ROS, relieve the antioxidant system disorder, and restrain the inflammation in HFD-induced obese mice, with good biocompatibility. After 30 days of Au22 clusterzymes treatment, high therapeutic efficacy in anti-obesity is observed in HFD-induced obese mice, including decreased body weight by 13%, reduced serum levels of key inflammatory factors (IL-1β, IL-6, and TNF-α) in the obese mice by 23 – 48%, improved glucose tolerance and lipid metabolism, and increased browning of white adipose tissue (WAT). Overall, Au22 clusterzymes have good performance on ROS-scavenging and anti-inflammation in vivo, offering a promising approach to combat obesity and related metabolic diseases.

Irisin promotes tilapia muscle cell growth and amino acid uptake via IGF-1 signaling.

Irisin is a recently discovered myokine that facilitates the browning of white adipose tissue, increases glucose uptake in skeletal muscle, and influences metabolic processes in the liver. However, its potential effects on amino acid absorption remained largely unexplored. This study aimed to elucidate the role of irisin in modulating amino acid uptake and delineate the underlying molecular mechanisms involved. To this end, juvenile tilapia were administered intraperitoneal irisin injections at 100 ng/g body weight over 8 weeks. Evaluation of various physiological parameters revealed that irisin supplementation significantly improved the specific growth rate and feed conversion efficiency while reducing feed consumption. Muscle tissue analysis revealed that irisin significantly modified the proximate composition by increasing protein content and reducing lipid levels. It also significantly raised the levels of both essential and non-essential amino acids in the muscle. Histological analysis demonstrated that irisin-stimulated muscle growth through hyperplasia rather than hypertrophy, corroborated by upregulated IGF-1 mRNA and downregulated myostatin mRNA expression. Mechanistic studies in cultured tilapia muscle cells elucidated that irisin activated integrin receptors on muscle cells, which subsequently engaged IGF-1/IGF-1R signaling. Downstream of IGF-1R activation, irisin simultaneously stimulates the ERK1/2 and PI3K/mTORC2/Akt pathways. The convergence of these pathways upregulates L-type amino acid transporter 1 expression, thereby augmenting amino acid uptake into muscle cells. In summary, irisin supplementation in tilapia leads to improved muscle growth, predominantly via hyperplasia and augmented amino acid assimilation, governed by intricate cellular signaling pathways. These findings provide valuable aquaculture applications and novel insights into muscle development.

Neuregulin4-ErbB4 signalling pathway is driven by electroacupuncture stimulation to remodel brown adipose tissue innervation.

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. 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. 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. 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.

Non-invasive mapping of brown adipose tissue activity with magnetic resonance imaging

Thermogenic brown adipose tissue (BAT) has a positive impact on whole-body metabolism. However, in vivo mapping of BAT activity typically relies on techniques involving ionizing radiation, such as [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) and computed tomography (CT). Here we report a noninvasive metabolic magnetic resonance imaging (MRI) approach based on creatine chemical exchange saturation transfer (Cr-CEST) contrast to assess in vivo BAT activity in rodents and humans. In male rats, a single dose of the β3-adrenoceptor agonist (CL 316,243) or norepinephrine, as well as cold exposure, triggered a robust elevation of the Cr-CEST MRI signal, which was consistent with the [18F]FDG PET and CT data and 1H nuclear magnetic resonance measurements of creatine concentration in BAT. We further show that Cr-CEST MRI detects cold-stimulated BAT activation in humans (both males and females) using a 3T clinical scanner, with data-matching results from [18F]FDG PET and CT measurements. This study establishes Cr-CEST MRI as a promising noninvasive and radiation-free approach for in vivo mapping of BAT activity.

Overexpression of PRDM16 improves muscle function after rotator cuff tears

Muscle atrophy, fibrosis, and fatty infiltration are commonly seen in rotator cuff tears (RCTs), which are critical factors that directly determine the clinical outcomes for patients with this injury. Therefore, improving muscle quality after RCT is crucial in improving the clinical outcome of tendon repair. In recent years, it has been discovered that adults have functional beige/brown adipose tissue (BAT) that can secrete batokines to promote muscle growth. PRDM16, a PR-domain-containing protein, was discovered with the ability to determine the brown fat cell fate and stimulate its development. Thus, the goal of this study was to discover the role of PRDM16 in improving muscle function after massive tendon tears using a transgenic mouse model with an elevated level of PRDM16 expression. Transgenic aP2-driven PRDM16-overexpressing mice and C57BL/6J mice underwent unilateral supraspinatus (SS) tendon transection and suprascapular nerve transection (TTDN) as described previously (n=8 in each group). DigiGait was performed to evaluate forelimb function at 6 weeks post the TTDN injury. Bilateral SS muscles, interscapular brown fat, epididymal white fat, and inguinal beige fat were harvested for analysis. The expression of PRDM16 in adipose tissue was detected by Western blot. Masson Trichrome staining was conducted to evaluate the muscle fibrosis, and Oil Red O staining was used to determine the fat infiltration. Muscle fiber type was determined by major histocompatibility complex (MHC) expression via immunostaining. All data were presented in the form of mean±standard deviation. t test and 2-way analysis of variance was performed to determine a statistically significant difference between groups. Significance was considered when P<.05. Western blot data showed an increased expression of PRDM16 protein in both white and brown fat in PRDM16-overexpressing mice compared with wild-type (WT) mice. Even though PRDM16 overexpression had no effect on increasing muscle weight, it significantly improved the forelimbs function with longer brake, stance, and stride time and larger stride length and paw area in mice after RCT. Additionally, PRDM16-overexpressing mice showed no difference in the amount of fibrosis when compared to WT mice; however, they had a significantly reduced area of fatty infiltration. These mice also exhibited abundant MHC-IIx fiber percentage in the supraspinatus muscle after TTDN. Overexpression of PRDM16 significantly improved muscle function and reduced fatty infiltration after rotator cuff tears. Promoting BAT activity is beneficial in improving rotator cuff muscle quality and shoulder function after RCT.

White adipocytes in subcutaneous fat depots require KLF15 for maintenance in preclinical models.

Healthy adipose tissue is essential for normal physiology. There are 2 broad types of adipose tissue depots: brown adipose tissue (BAT), which contains adipocytes poised to burn energy through thermogenesis, and white adipose tissue (WAT), which contains adipocytes that store lipids. However, within those types of adipose, adipocytes possess depot and cell-specific properties that have important implications. For example, the subcutaneous and visceral WAT confers divergent risk for metabolic disease. Further, within a depot, different adipocytes can have distinct properties; subcutaneous WAT can contain adipocytes with either white or brown-like (beige) adipocyte properties. However, the pathways that regulate and maintain this cell and depot-specificity are incompletely understood. Here, we found that the transcription factor KLF15 is required for maintaining white adipocyte properties selectively within the subcutaneous WAT. We revealed that deletion of Klf15 is sufficient to induce beige adipocyte properties and that KLF15's direct regulation of Adrb1 is a critical molecular mechanism for this process. We uncovered that this activity is cell autonomous but has systemic implications in mouse models and is conserved in primary human adipose cells. Our results elucidate a pathway for depot-specific maintenance of white adipocyte properties that could enable the development of therapies for obesity and associated diseases.

Chronic Alcohol Consumption Impairs BCAA Catabolism in Brown Fat

Chronic Alcohol Consumption Impairs BCAA Catabolism in Brown Fat

The Effect of KSK-94, a Dual Histamine H3 and Sigma-2 Receptor Ligand, on Adipose Tissue in a Rat Model of Developing Obesity.

Numerous studies highlight the critical role that neural histamine plays in feeding behavior, which is controlled by central histamine H3 and H1 receptors. This is the fundamental motivation for the increased interest in creating histamine H3 receptor antagonists as anti-obesity medications. On the other hand, multiple other neurotransmitter systems have been identified as pharmacotherapeutic targets for obesity, including sigma-2 receptor systems. Interestingly, in our previous studies in the rat excessive eating model, we demonstrated a significant reduction in the development of obesity using dual histamine H3/sigma-2 receptor ligands. Moreover, we showed that compound KSK-94 (structural analog of Abbott's A-331440) reduced the number of calories consumed, and thus acted as an anorectic compound. Therefore, in this study, we extended the previous research and studied the influence of KSK-94 on adipose tissue collected from animals from our previous experiment. Visceral adipose tissue was collected from four groups of rats (standard diet + vehicle, palatable diet + vehicle, palatable diet + KSK-94, and palatable diet + bupropion/naltrexone) and subjected to biochemical, histopathological, and immunohistochemical studies. The obtained results clearly indicate that compound KSK-94 prevented the hypertrophy and inflammation of visceral adipose tissue, normalized the levels of leptin, resistin and saved the total reduction capacity of adipose tissue, being more effective than bupropion/naltrexon in these aspects. Moreover, KSK-94 may induce browning of visceral white adipose tissue. Our study suggests that dual compounds with a receptor profile like KSK-94, i.e., targeting histamine H3 receptor and, to a lesser extent, sigma-2 receptor, could be attractive therapeutic options for patients at risk of developing obesity or with obesity and some metabolic disorders. However, more studies are required to determine its safety profile and the exact mechanism of action of KSK-94.

Differential expression of ADRB1 causes different responses to norepinephrine in adipocytes of Duroc-Landrace-Yorkshire pigs and min pigs

Research has shown that pigs from different regions exhibit varying responses to cold stimuli. Typically, cold stimuli induce browning of white adipose tissue mediated by adrenaline, promoting non-shivering thermogenesis. However, the molecular mechanisms underlying differential response of pig breeds to norepinephrine are unclear.The aim of this study was to investigate the differences and molecular mechanisms of the effects of norepinephrine (NE) treatment on adipocytes of Min pigs (a cold-resistant pig breed) and Duroc-Landrace-Yorkshire (DLY) pigs. Real time-qPCR, western blot, and immunofluorescence were performed following NE treatment on cell cultures of adipocytes originating from Min pigs (n = 3) and DLY pigs (n = 3) to assess the expressions of adipogenesis markers, beige fat markers, and mitochondrial biogenesis markers. The results showed that NE did not affect browning of adipocytes in DLY pigs, whereas promoted browning of adipocytes in Min pigs. Further, the expression of ADRB1 (Adrenoceptor Beta 1, ADRB1) was higher in subcutaneous adipose tissue and adipocytes of Min pigs than those of DLY pigs. Overexpression of ADRB1 in DLY pig adipocytes enhanced sensitivity to NE, exhibiting decreased adipogenesis markers, upregulated beige fat markers, and increased mitochondrial biogenesis. Conversely, adipocytes treated with ADRB1 antagonist in Min pigs resulted in decreased cellular sensitivity to NE. Further studies revealed differential CpG island methylation in ADRB1 promoter region, with lower methylation levels in Min pigs compared to DLY pigs. In conclusion, differential methylation of the ADRB1 promoter region leads to different ADRB1 expression, resulting in varying responsiveness to NE in adipocytes of two pig breeds. Our results provide new insights for further analysis of the differential cold responsiveness in pig breeds from different regions.

[18F]F-AraG imaging reveals association between neuroinflammation and brown- and bone marrow adipose tissue

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.

The role of brown adipose tissue in metabolic health.

The role of brown adipose tissue in metabolic health.

The Role of FGF21 in High-Fat Diet-Induced Alterations in Brown Adipose Tissue Metabolism

The Role of FGF21 in High-Fat Diet-Induced Alterations in Brown Adipose Tissue Metabolism