Abstract
Beige adipocytes are a new type of recruitable brownish adipocytes, with highly mitochondrial membrane uncoupling protein 1 expression and thermogenesis. Beige adipocytes were found among white adipocytes, especially in subcutaneous white adipose tissue (sWAT). Therefore, beige adipocytes may be involved in the regulation of energy metabolism and fat deposition. Transient receptor potential melastatin 8 (TRPM8), a Ca2+-permeable non-selective cation channel, plays vital roles in the regulation of various cellular functions. It has been reported that TRPM8 activation enhanced the thermogenic function of brown adiposytes. However, the involvement of TRPM8 in the thermogenic function of WAT remains unexplored. Our data revealed that TRPM8 was expressed in mouse white adipocytes at mRNA, protein and functional levels. The mRNA expression of Trpm8 was significantly increased in the differentiated white adipocytes than pre-adipocytes. Moreover, activation of TRPM8 by menthol enhanced the expression of thermogenic genes in cultured white aidpocytes. And menthol-induced increases of the thermogenic genes in white adipocytes was inhibited by either KT5720 (a protein kinase A inhibitor) or BAPTA-AM. In addition, high fat diet (HFD)-induced obesity in mice was significantly recovered by co-treatment with menthol. Dietary menthol enhanced WAT “browning” and improved glucose metabolism in HFD-induced obesity mice as well. Therefore, we concluded that TRPM8 might be involved in WAT “browning” by increasing the expression levels of genes related to thermogenesis and energy metabolism. And dietary menthol could be a novel approach for combating human obesity and related metabolic diseases.
Highlights
Obesity is a serious health problem that is implicated in various diseases including type II diabetes, hypertension, coronary heart diseases and cancer [1], and it is characterized by increased adipose tissue mass that results from increased fat cell size and number, suggesting that the main contributor to obesity is adipose tissue [2]
We observed that the mRNA expression of peroxisome proliferatoractivated receptor γ (Pparγ) was significantly increased in the www.impactjournals.com/oncotarget differentiated white adipocytes than in pre-adipocytes from mouse subcutaneous white adipose tissue (sWAT) (Figure 1B)
white adipose tissue (WAT) is the primary depot for energy storage in mammals [32] and brown adipose tissue (BAT) is an important component in whole-body energy homeostasis through the dissipation of stored chemical energy in the form of heat [33]
Summary
Obesity is a serious health problem that is implicated in various diseases including type II diabetes, hypertension, coronary heart diseases and cancer [1], and it is characterized by increased adipose tissue mass that results from increased fat cell size and number, suggesting that the main contributor to obesity is adipose tissue [2]. It has been reported that a new type of recruitable brownish adipocytes, termed “beige adipocytes”, was found among white adipocytes, especially in subcutaneous WAT (sWAT) [6]. Beige adipocytes are recruited especially after a short-term cold challenge or giving a β3-adrenergic receptor agonist treatment, which are very similar to brown adipocytes, with highly mitochondrial membrane uncoupling protein 1 (UCP1) expression and thermogenesis [7, 8]. This novel finding highlights the crucial role for beige cells in the regulation of energy metabolism and fat deposition. Enhancing of beige adipocytes activity in WAT could be a promising target for the prevention and therapy of human obesity, and understanding the molecular mechanisms for thermogenesis in “beige adipocytes” is the subject of intense investigation
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