Role of Thermo-Sensitive Transient Receptor Potential Channels in Brown Adipose Tissue

Kunitoshi Uchida, Wuping Sun, Jun Yamazaki, Makoto Tominaga
2018 Biological and Pharmaceutical Bulletin  
Brown and beige adipocytes are a major site of mammalian non-shivering thermogenesis and energy dissipation. Obesity is caused by an imbalance between energy intake and expenditure and has become a worldwide health problem. Therefore modulation of thermogenesis in brown and beige adipocytes could be an important application for body weight control and obesity prevention. Over the last few decades, the involvement of thermo-sensitive transient receptor potential (TRP) channels (including TRPV1,
more » ... (including TRPV1, TRPV2, TRPV3, TRPV4, TRPM4, TRPM8, TRPC5, and TRPA1) in energy metabolism and adipogenesis in adipocytes has been extensively explored. In this review, we summarize the expression, function, and pathological/ physiological contributions of these TRP channels and discuss their potential as future therapeutic targets for preventing and combating human obesity and obesity-related metabolic disorders. these tissues, especially adipose tissue, has recently been reported. BROWN AND BEIGE ADIPOSE TISSUE AND ENERGY METABOLISM Brown and Beige Adipose Tissue Adipose tissue is a highly specialized tissue that plays a key role in energy homeostasis. 22) There are two types of adipose tissue in mammals, termed "white adipose tissue" (WAT) and "brown adipose tissue" (BAT). Recently, a new type of recruitable brownish adipocytes, termed "beige adipocytes" (also known as "brite adipocytes"), was discovered among white adipocytes, especially in subcutaneous WAT. 23) Beige adipocytes are induced by sympathetic nerve activation after cold exposure or by treatment with β 3 -adrenergic receptor agonists. Beige adipocytes also have many mitochondria and small lipid droplets. Although a proportion of the gene expression profile in beige adipocytes is different from that in brown adipocytes, beige adipocytes have mitochondrial uncoupling protein 1 (UCP1) expression and high ability of thermogenesis. 24, 25) The functions of WAT and BAT are almost the opposite of one another in terms of their function in energy metabolism. While WAT is a tissue for energy storage as lipid droplets, the main function of BAT is energy expenditure. 26,27) BAT is a major tissue for mammalian non-shivering thermogenesis via activation of mitochondrial UCP1, a physiological process during which heat production increases in response to body temperature changes. 28, 29) The release of norepinephrine from sympathetic nerve terminals after sensory nerve activation by cold exposure or vagus nerve activation by intake of pungents is the initial thermogenesis, 30,31) followed by UCP1 activation and increase in H + conductance in the mitochondria. While it is uncertain whether non-shivering thermogenesis in BAT occurs in human, studies using fluorodeoxyglucose (FDG)positron emission tomography (PET) in combination with computed tomography (CT) techniques have revealed that BAT is also found in adult humans. 32,33) A histological study also demonstrated that some adipocytes express UCP1 in human adipose tissue. 23) Moreover, the gene expression profile in BAT suggests that human BAT might be heterogeneous, containing not only white and brown adipocytes but also beige adipocytes. [34] [35] [36] Obesity is recognized as a serious global health problem 37) and is believed to result from an imbalance between energy intake and energy expenditure. 38) Considerable evidence has demonstrated that BAT is involved in the long-term regulation of energy metabolism and body fat mass. By measuring oxygen consumption, BAT thermogenesis was found decreased in obese mice. 39,40) Long-term cold stimulation and/or β 3adrenergic receptor agonist treatment decreased the amount of body fat associated with BAT hyperplasia. 27,41) Furthermore, it was reported that UCP1 knockout mice became obese following treatment with a high-fat diet (HFD) for longer than 6 months. 42) Several studies have also reported an inverse relationship between BAT activity/amount and obesity-related parameters, such as body fat content and body mass index (BMI) in humans. 32, 43, 44) Thus activation of thermogenesis in BAT could be a means of prevention or attenuation of obesity and the obesity-related metabolic syndrome. Mechanism of Thermogenesis in Brown and Beige
doi:10.1248/bpb.b18-00063 pmid:30068861 fatcat:3dyukpypu5af7b7ucspli4wsse