Dietary menthol-induced TRPM8 activation enhances WAT “browning” and ameliorates diet-induced obesity

Abstract

// Changyu Jiang 1, * , Mingzhu Zhai 2, * , Dong Yan 1 , Da Li 3 , Chen Li 4 , Yonghong Zhang 4 , Lizu Xiao 1 , Donglin Xiong 1 , Qiwen Deng 5 and Wuping Sun 1 1 Department of Pain Medicine and Shenzhen Municipal Key Laboratory for Pain Medicine, The Affiliated Nanshan People’s Hospital of Shenzhen University, Shenzhen Municipal Sixth People’s Hospital, Shenzhen 518060, China 2 Institute of Science and Technology Austria, Am Campus 1, Klosterneuburg 3400, Austria 3 Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, China 4 Laboratory of Medicinal Plant, School of Basic Medicine, Laboratory of Chinese Herbal Pharmacology, Oncology Center, Renmin Hospital and Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Hubei University of Medicine, Hubei 442000, China 5 Department of Infectious Diseases and Shenzhen Municipal Key Laboratory for Endogenous Infection, The Affiliated Nanshan People’s Hospital of Shenzhen University, Shenzhen Municipal Sixth People’s Hospital, Shenzhen 518060, China * These authors have contributed equally to this work Correspondence to: Wuping Sun, email: wuping.sun@foxmail.com Keywords: WAT, beige adipocytes, thermogenesis, browning, obesity Received: January 31, 2017     Accepted: July 29, 2017     Published: August 24, 2017 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 Ca 2+ -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.