Overexpression of Adiponectin Receptor 1 Inhibits Brown and Beige Adipose Tissue Activity in Mice

Adult humans and mice possess significant classical brown adipose tissues (BAT) and, upon cold-induction, acquire brown-like adipocytes in certain depots of white adipose tissues (WAT), known as beige adipose tissues or WAT browning/beiging. Activating thermogenic classical BAT or WAT beiging to generate heat limits diet-induced obesity or type-2 diabetes in mice. Adiponectin is a beneficial adipokine resisting diabetes, and causing “healthy obese” by increasing WAT expansion to limit lipotoxicity in other metabolic tissues during high-fat feeding. However, the role of its receptors, especially adiponectin receptor 1 (AdipoR1), on cold-induced thermogenesis in vivo in BAT and in WAT beiging is still elusive. Here, we established a cold-induction procedure in transgenic mice over-expressing AdipoR1 and applied a live 3-D [¹⁸F] fluorodeoxyglucose-PET/CT (¹⁸F-FDG PET/CT) scanning to measure BAT activity by determining glucose uptake in cold-acclimated transgenic mice. Results showed that cold-acclimated mice over-expressing AdipoR1 had diminished cold-induced glucose uptake, enlarged adipocyte size in BAT and in browned WAT, and reduced surface BAT/body temperature in vivo. Furthermore, decreased gene expression, related to thermogenic Ucp1, BAT-specific markers, BAT-enriched mitochondrial markers, lipolysis and fatty acid oxidation, and increased expression of whitening genes in BAT or in browned subcutaneous inguinal WAT of AdipoR1 mice are congruent with results of PET/CT scanning and surface body temperature in vivo. Moreover, differentiated brown-like beige adipocytes isolated from pre-adipocytes in subcutaneous WAT of transgenic AdipoR1 mice also had similar effects of lowered expression of thermogenic Ucp1, BAT selective markers, and BAT mitochondrial markers. Therefore, this study combines in vitro and in vivo results with live 3-D scanning and reveals one of the many facets of the adiponectin receptors in regulating energy homeostasis, especially in the involvement of cold-induced thermogenesis.     

miR-143-null Is against Diet-Induced Obesity by Promoting BAT Thermogenesis and Inhibiting WAT Adipogenesis

Excessive energy intake is the main cause of obesity, and stimulation of brown adipose tissue (BAT) thermogenesis has emerged as an attractive tool for anti-obesity. Although miR-143 has been reported to promote white adipocyte differentiation, its role in BAT remains unclear. In our study, we found that during HFD-induced obesity, the expression of miR-143 in BAT was significantly reduced, and the expression of miR-143 in WAT first increased and then decreased. Knockout (KO) of miR-143 with CRISPR/Cas9 did not affect the energy metabolism of normal diet fed mice and brown adipocyte differentiation but inhibited the differentiation of white adipocytes. Importantly, during high fat diet-induced obesity, miR-143KO significantly reduced body weight, and improved energy expenditure, insulin sensitivity, and glucose tolerance. Further exploration showed that miR-143KO reduced the weight of adipose tissue, promoted mitochondrial number and functions, induced thermogenesis and lipolysis of BAT, increased lipolysis, and inhibited lipogenesis of white adipose tissue (WAT). Our study considerably improves our collective understanding of the function of miR-143 in adipose tissue and its potential significance in anti-obesity and provides a new avenue for the management of obesity through the inhibition of miR-143 in BAT and WAT.     

Potential of Nutraceutical Supplementation in the Modulation of White and Brown Fat Tissues in Obesity-Associated Disorders: Role of Inflammatory Signalling

The high incidence of obesity is associated with an increasing risk of several chronic diseases such as cardiovascular disease, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Sustained obesity is characterized by a chronic and unsolved inflammation of adipose tissue, which leads to a greater expression of proinflammatory adipokines, excessive lipid storage and adipogenesis. The purpose of this review is to clarify how inflammatory mediators act during adipose tissue dysfunction in the development of insulin resistance and all obesity-associated diseases. In particular, we focused our attention on the role of inflammatory signaling in brown adipose tissue (BAT) thermogenic activity and the browning of white adipose tissue (WAT), which represent a relevant component of adipose alterations during obesity. Furthermore, we reported the most recent evidence in the literature on nutraceutical supplementation in the management of the adipose inflammatory state, and in particular on their potential effect on common inflammatory mediators and pathways, responsible for WAT and BAT dysfunction. Although further research is needed to demonstrate that targeting pro-inflammatory mediators improves adipose tissue dysfunction and activates thermogenesis in BAT and WAT browning during obesity, polyphenols supplementation could represent an innovative therapeutic strategy to prevent progression of obesity and obesity-related metabolic diseases.     

Role of Brown and Beige Adipose Tissues in Seasonal Adaptation in the Raccoon Dog (Nyctereutes procyonoides)

Brown adipose tissue (BAT) expresses uncoupling protein-1 (UCP1), which enables energy to be exerted towards needed thermogenesis. Beige adipocytes are precursor cells interspersed among white adipose tissue (WAT) that possess similar UCP1 activity and capacity for thermogenesis. The raccoon dog (Nyctereutes procyonoides) is a canid species that utilizes seasonal obesity to survive periods of food shortage in climate zones with cold winters. The potential to recruit a part of the abundant WAT storages as beige adipocytes for UCP1-dependent thermogenesis was investigated in vitro by treating raccoon dog adipocytes with different browning inducing factors. In vivo positron emission tomography/computed tomography (PET/CT) imaging with the glucose analog ¹⁸F-FDG showed that BAT was not detected in the adult raccoon dog during the winter season. In addition, UCP1 expression was not changed in response to chronic treatments with browning inducing factors in adipocyte cultures. Our results demonstrated that most likely the raccoon dog endures cold weather without the induction of BAT or recruitment of beige adipocytes for heat production. Its thick fur coat, insulating fat, and muscle shivering seem to provide the adequate heat needed for surviving the winter.     

Brown Adipose Tissue and Its Role in Insulin and Glucose Homeostasis

The increased worldwide prevalence of obesity, insulin resistance, and their related metabolic complications have prompted the scientific world to search for new possibilities to combat obesity. Brown adipose tissue (BAT), due to its unique protein uncoupling protein 1 (UPC1) in the inner membrane of the mitochondria, has been acknowledged as a promising approach to increase energy expenditure. Activated brown adipocytes dissipate energy, resulting in heat production. In other words, BAT burns fat and increases the metabolic rate, promoting a negative energy balance. Moreover, BAT alleviates metabolic complications like dyslipidemia, impaired insulin secretion, and insulin resistance in type 2 diabetes. The aim of this review is to explore the role of BAT in total energy expenditure, as well as lipid and glucose homeostasis, and to discuss new possible activators of brown adipose tissue in humans to treat obesity and metabolic disorders.     

Molecular and Physiological Effects of Browning Agents on White Adipocytes from Bone Marrow Mesenchymal Stromal Cells

Two different types of adipose depots can be observed in mammals: white adipose tissue (WAT) and brown adipose tissue (BAT). The primary role of WAT is to deposit surplus energy in the form of triglycerides, along with many metabolic and hormonal activities; as thermogenic tissue, BAT has the distinct characteristic of using energy and glucose consumption as a strategy to maintain the core body temperature. Under specific stimuli—such as exercise, cold exposure, and drug treatment—white adipocytes can utilize their extraordinary flexibility to transdifferentiate into brown-like cells, called beige adipocytes, thereby acquiring new morphological and physiological characteristics. For this reason, the process is identified as the ‘browning of WAT’. We evaluated the ability of some drugs, including {"type":"entrez-nucleotide","attrs":{"text":"GW501516","term_id":"289075981"}}GW501516, sildenafil, and rosiglitazone, to induce the browning process of adult white adipocytes obtained from differentiated mesenchymal stromal cells (MSCs). In addition, we broadened our investigation by evaluating the potential browning capacity of IRISIN, a myokine that is stimulated by muscular exercises. Our data indicate that IRISIN was effective in promoting the browning of white adipocytes, which acquire increased expression of UCP1, increased mitochondrial mass, and modification in metabolism, as suggested by an increase of mitochondrial oxygen consumption, primarily in presence of glucose as a nutrient. These promising browning agents represent an appealing focus in the therapeutic approaches to counteracting metabolic diseases and their associated obesity.     

DEPP Deficiency Contributes to Browning of White Adipose Tissue

Decidual protein induced by progesterone (DEPP) was originally identified as a modulator in the process of decidualization in the endometrium. Here, we define that DEPP is involved in adipose tissue thermogenesis, which contributes to metabolic regulation. Knockdown of DEPP suppressed adipocyte differentiation and lipid accumulation in 3T3-L1 cells, induced expression of brown adipose tissue (BAT) markers in primary brown adipocyte and induced mouse embryonic fibroblasts (MEFs) differentiation to brown adipocytes. Moreover, DEPP deficiency in mice induced white adipocyte browning and enhanced BAT activity. Cold exposure stimulated more browning of white adipose tissue (WAT) and maintained higher body temperature in DEPP knockout mice compared to that in wild-type control mice. DEPP deficiency also protected mice against high-fat-diet-induced insulin resistance. Mechanistic studies demonstrated that DEPP competitively binds SIRT1, inhibiting the interaction between peroxisome proliferator-activated receptor gamma (PPARγ) and Sirtuin 1 (SIRT1). Collectively, these findings suggest that DEPP plays a crucial role in orchestrating thermogenesis through regulating adipocyte programs and thus might be a potential target for the treatment of metabolic disorders.     

Factors Associated with White Fat Browning: New Regulators of Lipid Metabolism

Mammalian adipose tissue can be divided into white and brown adipose tissue based on its colour, location, and cellular structure. Certain conditions, such as sympathetic nerve excitement, can induce the white adipose adipocytes into a new type of adipocytes, known as beige adipocytes. The process, leading to the conversion of white adipocytes into beige adipocytes, is called white fat browning. The dynamic balance between white and beige adipocytes is closely related to the body’s metabolic homeostasis. Studying the signal transduction pathways of the white fat browning might provide novel ideas for the treatment of obesity and alleviation of obesity-related glucose and lipid metabolism disorders. This article aimed to provide an overview of recent advances in understanding white fat browning and the role of BAT in lipid metabolism.     

Uncoupling Protein 1 Does Not Produce Heat without Activation

Mitochondrial uncoupling protein 1 (UCP1) is the crucial mechanistic component of heat production in classical brown fat and the newly identified beige or brite fat. Thermogenesis inevitably comes at a high energetic cost and brown fat, ultimately, is an energy-wasting organ. A constrained strategy that minimizes brown fat activity unless obligate will have been favored during natural selection to safeguard metabolic thriftiness. Accordingly, UCP1 is constitutively inhibited and is inherently not leaky without activation. It follows that increasing brown adipocyte number or UCP1 abundance genetically or pharmacologically does not lead to an automatic increase in thermogenesis or subsequent metabolic consequences in the absence of a plausible route of concomitant activation. Despite its apparent obviousness, this tenet is frequently ignored. Consequently, incorrect conclusions are often drawn from increased BAT or brite/beige depot mass, e.g., predicting or causally linking beneficial metabolic effects. Here, we highlight the inherently inactive nature of UCP1, with a particular emphasis on the molecular brakes and releases of UCP1 activation under physiological conditions. These controls of UCP1 activity represent potential targets of therapeutic interventions to unlock constraints and efficiently harness the energy-expending potential of brown fat to prevent and treat obesity and associated metabolic disorders.     

Sexual Dimorphism in Brown Adipose Tissue Activation and White Adipose Tissue Browning

The present narrative review gathers the studies reported so far, addressing sex differences in the effects of cold exposure, feeding pattern and age on brown adipose tissue (BAT) thermogenesis and white adipose tissue (WAT) browning. In rodents, when exposed to decreasing temperatures, females activate thermogenesis earlier. Results obtained in humans go in the same line, although they do not provide results as solid as those obtained in rodents. Regarding the effects of overfeeding, interesting sex differences on BAT thermogenic capacity have been reported, and the greater or lower sensitivity of each sex to this dietary situation seems to be dependent on the type of feeding. In the case of energy restriction, females are more sensitive than males. In addition, sex differences have also been observed in thermogenesis changes induced by phenolic compound administration. During sexual development, an increase in BAT mass and BAT activity takes place. This phenomenon is greater in boys than in girls, probably due to its relation to muscle-mass growth. The opposite situation takes place during ageing, a lifespan period where thermogenic capacity declines, this being more acute in men than in women. Finally, the vast majority of the studies have reported a higher susceptibility to developing WAT browning amongst females. The scarcity of results highlights the need for further studies devoted to analysing this issue, in order to provide valuable information for a more personalised approach.     

Tissue Transglutaminase Knock-Out Preadipocytes and Beige Cells of Epididymal Fat Origin Possess Decreased Mitochondrial Functions Required for Thermogenesis

Beige adipocytes with thermogenic function are activated during cold exposure in white adipose tissue through the process of browning. These cells, similar to brown adipocytes, dissipate stored chemical energy in the form of heat with the help of uncoupling protein 1 (UCP1). Recently, we have shown that tissue transglutaminase (TG2) knock-out mice have decreased cold tolerance in parallel with lower utilization of their epididymal adipose tissue and reduced browning. To learn more about the thermogenic function of this fat depot, we isolated preadipocytes from the epididymal adipose tissue of wild-type and TG2 knock-out mice and differentiated them in the beige direction. Although differentiation of TG2 knock-out preadipocytes is phenotypically similar to the wild-type cells, the mitochondria of the knock-out beige cells have multiple impairments including an altered electron transport system generating lower electrochemical potential difference, reduced oxygen consumption, lower UCP1 protein content, and a higher portion of fragmented mitochondria. Most of these differences are present in preadipocytes as well, and the differentiation process cannot overcome the functional disadvantages completely. TG2 knock-out beige adipocytes produce more iodothyronine deiodinase 3 (DIO3) which may inactivate thyroid hormones required for the establishment of optimal mitochondrial function. The TG2 knock-out preadipocytes and beige cells are both hypometabolic as compared with the wild-type controls which may also be explained by the lower expression of solute carrier proteins SLC25A45, SLC25A47, and SLC25A42 which transport acylcarnitine, Co-A, and amino acids into the mitochondrial matrix. As a consequence, the mitochondria in TG2 knock-out beige adipocytes probably cannot reach the energy-producing threshold required for normal thermogenic functions, which may contribute to the decreased cold tolerance of TG2 knock-out mice.     

Brown Adipose Tissue Sheds Extracellular Vesicles That Carry Potential Biomarkers of Metabolic and Thermogenesis Activity Which Are Affected by High Fat Diet Intervention

Brown adipose tissue (BAT) is a key target for the development of new therapies against obesity due to its role in promoting energy expenditure; BAT secretory capacity is emerging as an important contributor to systemic effects, in which BAT extracellular vesicles (EVs) (i.e., batosomes) might be protagonists. EVs have emerged as a relevant cellular communication system and carriers of disease biomarkers. Therefore, characterization of the protein cargo of batosomes might reveal their potential as biomarkers of the metabolic activity of BAT. In this study, we are the first to isolate batosomes from lean and obese Sprague–Dawley rats, and to establish reference proteome maps. An LC-SWATH/MS analysis was also performed for comparisons with EVs secreted by white adipose tissue (subcutaneous and visceral WAT), and it showed that 60% of proteins were exclusive to BAT EVs. Precisely, batosomes of lean animals contain proteins associated with mitochondria, lipid metabolism, the electron transport chain, and the beta-oxidation pathway, and their protein cargo profile is dramatically affected by high fat diet (HFD) intervention. Thus, in obesity, batosomes are enriched with proteins involved in signal transduction, cell communication, the immune response, inflammation, thermogenesis, and potential obesity biomarkers including UCP1, Glut1, MIF, and ceruloplasmin. In conclusion, the protein cargo of BAT EVs is affected by the metabolic status and contains potential biomarkers of thermogenesis activity.     

The Potential to Fight Obesity with Adipogenesis Modulating Compounds

Obesity is an increasingly severe public health problem, which brings huge social and economic burdens. Increased body adiposity in obesity is not only tightly associated with type 2 diabetes, but also significantly increases the risks of other chronic diseases including cardiovascular diseases, fatty liver diseases and cancers. Adipogenesis describes the process of the differentiation and maturation of adipocytes, which accumulate in distributed adipose tissue at various sites in the body. The major functions of white adipocytes are to store energy as fat during periods when energy intake exceeds expenditure and to mobilize this stored fuel when energy expenditure exceeds intake. Brown/beige adipocytes contribute to non-shivering thermogenesis upon cold exposure and adrenergic stimulation, and thereby promote energy consumption. The imbalance of energy intake and expenditure causes obesity. Recent interest in epigenetics and signaling pathways has utilized small molecule tools aimed at modifying obesity-specific gene expression. In this review, we discuss compounds with adipogenesis-related signaling pathways and epigenetic modulating properties that have been identified as potential therapeutic agents which cast some light on the future treatment of obesity.     

Exercise-Induced Adipose Tissue Thermogenesis and Browning: How to Explain the Conflicting Findings?

Brown adipose tissue (BAT) has been widely studied in targeting against metabolic diseases such as obesity, type 2 diabetes and insulin resistance due to its role in nutrient metabolism and energy regulation. Whether exercise promotes adipose tissue thermogenesis and browning remains controversial. The results from human and rodent studies contradict each other. In our opinion, fat thermogenesis or browning promoted by exercise should not be a biomarker of health benefits, but an adaptation under the stress between body temperature regulation and energy supply and expenditure of multiple organs. In this review, we discuss some factors that may contribute to conflicting experimental results, such as different thermoneutral zones, gender, training experience and the heterogeneity of fat depots. In addition, we explain that a redox state in cells potentially causes thermogenesis heterogeneity and different oxidation states of UCP1, which has led to the discrepancies noted in previous studies. We describe a network by which exercise orchestrates the browning and thermogenesis of adipose tissue with total energy expenditure through multiple organs (muscle, brain, liver and adipose tissue) and multiple pathways (nerve, endocrine and metabolic products), providing a possible interpretation for the conflicting findings.     

Androgen Reduces Mitochondrial Respiration in Mouse Brown Adipocytes: A Model for Disordered Energy Balance in Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is a common endocrinopathy that is associated with an adverse metabolic profile including reduced postprandial thermogenesis. Although abnormalities in adipose tissue function have been widely reported in women with PCOS, less is known about direct effects of androgen on white and, particularly, brown adipocytes. The purpose of this study was to investigate the effect of the nonaromatizable androgen dihydrotestosterone (DHT) on (1) lipid accumulation and expression of adipogenic markers in immortalized mouse brown adipose cell lines (IMBATs), (2) mitochondrial respiration in IMBATs, (3) mitochondrial DNA content and gene expression, (4) expression of brown adipose tissue (BAT) markers and thermogenic activation. In addition, we profiled the relative levels of 38 adipokines secreted from BAT explants and looked at androgen effects on adipokine gene expression in both IMBATs and immortalized mouse white adipose (IMWATs) cell lines. Androgen treatment inhibited IMBAT differentiation in a dose-dependent manner, reduced markers of adipogenesis, and attenuated the β-adrenoceptor-stimulated increase in uncoupling protein-1 (UCP1) expression. In explants of mouse interscapular BAT, androgen reduced expression of UCP1, peroxisome proliferator-activated receptor-γ coactivator-1 (PCG-1) and Cidea. Significantly, as well as affecting genes involved in thermogenesis in BAT, androgen treatment reduced mitochondrial respiration in IMBATs, as measured by the Seahorse XF method. The results of this study suggest a role for excess androgen in inhibiting brown adipogenesis, attenuating the activation of thermogenesis and reducing mitochondrial respiration in BAT. Together, these data provide a plausible molecular mechanism that may contribute to reduced postprandial thermogenesis and the tendency to obesity in women with PCOS.     

The Effect of a Sustained High-Fat Diet on the Metabolism of White and Brown Adipose Tissue and Its Impact on Insulin Resistance: A Selected Time Point Cross-Sectional Study

(1) Background: studies on the long-term dynamic changes in fat depot metabolism in response to a high-fat diet (HFD) on hepatic lipid deposition and insulin resistance are sparse. This study investigated the dynamic changes produced by HFD and the production of dysfunctional fat depots on insulin resistance and liver lipid metabolism. (2) Methods: mice fed a chow or HFD (45% kcal fat) diet had three fat depots, liver, and blood collected at 6, 10, 20, and 30 weeks. Anthropometric changes and gene markers for adipogenesis, thermogenesis, ECM remodeling, inflammation, and tissue insulin resistance were measured. (3) Results: early responses to the HFD were increased body weight, minor deposition of lipid in liver, increased adipocyte size, and adipogenesis. Later changes were dysfunctional adipose depots, increased liver fat, insulin resistance (shown by changes in ITT) accompanied by increased inflammatory markers, increased fibrosis (fibrosis > 2-fold, p < 0.05 from week 6), and the presence of crown cells in white fat depots. Later, changes did not increase thermogenic markers in response to the increased calories and decreased UCP1 and PRDM16 proteins in WAT. (4) Conclusions: HFD feeding initially increased adipocyte diameter and number, but later changes caused adipose depots to become dysfunctional, restricting adipose tissue expansion, changing the brown/beige ratios in adipose depots, and causing ectopic lipid deposition and insulin resistance.     

Lipid metabolism during cold-exposure and during cold-acclimation

The lipid-containing tissues are important in cold-exposure (exposure to cold of animals not previously living in the cold) and in cold-acclimation (the adaptive state achieved when animals have lived in the cold for several weeks); these are the white adipose tissue and the brown adipose tissue. The white adipose tissue serves as a store of readily mobilized substrate (free fatty acids [FFA]) for calorigenesis in other tissues during cold-exposure, principally for shivering thermogenesis in muscle. The mobilization of the sterol lipid is brought about through activation of the sympathetic nervous system by the cold stress. The brown adipose tissue has two functions in cold-exposure and in cold-adaptation, both quite distinct from the function of the white adipose tissue. These functions are heat production and the maintenance of the adaptationto cold. The triglycerides stored in the brown adipose tissue are mobilized as FFA, also via activation of the sympathetic nervous system, but the FFA are used primarily within the brown adipose tissue itself. The FFA are the agents which switch on the calorigenesis in the brown adipose tissue (via a poorly understood form of “loosening” of the coupling of oxidative phosphorylation); they also serve as the substrate for the calorigenesis. The heat-producing function of the brown adipose tissue occurs in both cold-exposed and in cold-acclimated animals; it is of greater importance in the latter because this tissue normally grows in response to cold. Much of the heat production in cold-acclimated animals (nonshivering thermogenesis) occurs outside the brown adipose tissue itself, most probably in the muscles, and the cold-acclimated animal differs from the cold-exposed animal in being able to switch on nonshivering thermogenesis via activation of the sympathetic nervous system. The maintenance of this adaptation for nonshivering thermogenesis in tissue other than the brown adipose tissue itself depends upon the brown adipose tissue. The adaptation disappears if the brown adipose tissue is removed; the adaptation does not develop if the normal proliferation of mitochondria in the growing brown adipose tissue is inhibited (with oxytetracycline) during acclimation of rats to cold. The mechanism by which the brown adipose tissue exerts this second function is at present unknown. An increased turnover of certain mitochondrial proteins occurs in those tissues (skeletal muscle and brown adipose tissue) in which nonshivering thermogenesis occurs in cold-acclimated rats; no change in turnover of mitochondrial proteins occurs in other tissues (liver and kidney). The relation of this alteration in mitochondrial proteins to the adaptation for nonshivering thermogenesis is at present unknown. However this first demonstration of a biochemical difference between skeletal muscle of cold-acclimated rats and skeletal muscle of warm-acclimated rats opens up a new approach to the study of the nature of both the adaptation for nonshivering thermogenesis and of the role of the brown adipose tissue in the development and maintenance of this adaptation. Presented at the Symposium on “Lipids in Metabolic Stress,” AOCS Fall Meeting, Atlantic City, October 1971. Bond Award paper. Award presented at the AOCS Spring Meeting, Los Angeles, April 1972.     

Genomic and Non-Genomic Actions of Glucocorticoids on Adipose Tissue Lipid Metabolism

Glucocorticoids (GCs) are hormones that aid the body under stress by regulating glucose and free fatty acids. GCs maintain energy homeostasis in multiple tissues, including those in the liver and skeletal muscle, white adipose tissue (WAT), and brown adipose tissue (BAT). WAT stores energy as triglycerides, while BAT uses fatty acids for heat generation. The multiple genomic and non-genomic pathways in GC signaling vary with exposure duration, location (adipose tissue depot), and species. Genomic effects occur directly through the cytosolic GC receptor (GR), regulating the expression of proteins related to lipid metabolism, such as ATGL and HSL. Non-genomic effects act through mechanisms often independent of the cytosolic GR and happen shortly after GC exposure. Studying the effects of GCs on adipose tissue breakdown and generation (lipolysis and adipogenesis) leads to insights for treatment of adipose-related diseases, such as obesity, coronary disease, and cancer, but has led to controversy among researchers, largely due to the complexity of the process. This paper reviews the recent literature on the genomic and non-genomic effects of GCs on WAT and BAT lipolysis and proposes research to address the many gaps in knowledge related to GC activity and its effects on disease.     

BMP7 Drives Human Adipogenic Stem Cells into Metabolically Active Beige Adipocytes

Adult humans have a substantial amount of inducible‐brown (or beige) fat, which is associated with increased energy expenditure and reduced weight gain via thermogenesis. Despite the identification of key regulators of beige adipogenesis, impacts of dietary factors on adaptive thermogenesis are largely unknown, partly due to a lack of validated human cell models. Bone morphogenetic protein 7 (BMP7) is known to promote brown adipogenesis in rodent and human progenitor cells. However, controversy still surrounds the cellular identity in BMP7‐mediated transition of white to brown adipocytes. The aim of this study was to confirm BMP7‐derived human adipocytes as a relevant in vitro model of human beige adipocyte by verifying the cellular lineage and metabolic activity. In this study, we hypothesized that pre‐exposure of the stromal vascular (SV) fraction of primary human adipogenic precursor cells (hASC) to BMP7 would convert metabolically active brown adipocytes. Our results showed that exposure of hASC to human BMP7 was associated with significant escalation of (1) UCP1 gene expression, a signature gene of brown adipocytes, (2) beige specific marker gene expression (i.e., CD137 and TMEM26), (3) glucose and fatty acid uptake, and (4) basal and cAMP‐stimulated oxygen consumption rate compared to white adipocyte control. Taken together, we demonstrated that BMP7 mediates conversion of hASC into metabolically active beige adipocytes. By confirming the cellular identity and metabolic activity, this BMP7‐induced human beige adipocytes from hASC should aid in the discovery and assessment of bioactive molecules to promote adaptive thermogenesis.