Abstract
Nonshivering thermogenesis is the process of biological heat production in mammals and is primarily mediated by brown adipose tissue (BAT). Through ubiquitous expression of uncoupling protein 1 (Ucp1) on the mitochondrial inner membrane, BAT displays uncoupling of fuel combustion and ATP production in order to dissipate energy as heat. Because of its crucial role in regulating energy homeostasis, ongoing exploration of BAT has emphasized its therapeutic potential in addressing the global epidemics of obesity and diabetes. The recent appreciation that adult humans possess functional BAT strengthens this prospect. Furthermore, it has been identified that there are both classical brown adipocytes residing in dedicated BAT depots and “beige” adipocytes residing in white adipose tissue depots that can acquire BAT-like characteristics in response to environmental cues. This review aims to provide a brief overview of BAT research and summarize recent findings concerning the physiological, cellular, and developmental characteristics of brown adipocytes. In addition, some key genetic, molecular, and pharmacologic targets of BAT/Beige cells that have been reported to have therapeutic potential to combat obesity will be discussed.
Highlights
Thermogenesis is the process of biological heat generation that plays a crucial role in the homeostatic regulation of body temperature in warm-blooded animals
PR domain containing 16 (Prdm16) haploinsufficiency reduces browning in white adipose tissue (WAT) when stimulated by β-adrenergic agonists. These results demonstrate that Prdm16 is a cell-autonomous determinant of the brown adipose tissue (BAT) gene program and thermogenesis in subcutaneous adipose tissues [40]
Pharmacological and plant-based browning agents β3AR agonist induces browning in WAT, strong response to cold in the form of increased thermogenesis, increased uncoupling protein 1 (Ucp1) mRNA in WAT and BAT upon treatment, weight loss, and improved energy expenditure
Summary
Thermogenesis is the process of biological heat generation that plays a crucial role in the homeostatic regulation of body temperature in warm-blooded animals. Similar to adipocytes in BAT, beige cells in mouse WAT are defined by their multilocular lipid droplet morphology, high mitochondrial content, and the expression of a core set of brown fat specific genes such as Ucp, Cidea, and peroxisome proliferator-activated receptorgamma coactivator (Pgc1α). PPARγ in the endothelium of BAT and vascular endothelial growth factor B (VEGF-B) in heart and skeletal muscle control the uptake of FAs to regulate and integrate vascular and metabolic responses adverse circumstances [17,18,19] The activity of these cells has been negatively associated with diet-induced obesity in animal models, while ablation or loss of function has resulted in increased susceptibility to diet-induced obesity. We will provide perspective on the current therapeutic potential of BAT/Beige cells to combat obesity
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