Referenced in: none

Automatically associated channels: TRP , TRPM , TRPM8

Title: Activation of the cold-sensing TRPM8 channel triggers UCP1-dependent thermogenesis and prevents obesity.

Authors: Shuangtao Ma, Hao Yu, Zhigang Zhao, Zhidan Luo, Jing Chen, Yinxing Ni, Rongbing Jin, Liqun Ma, Peijian Wang, Zhenyu Zhu, Li Li, Jian Zhong, Daoyan Liu, Bernd Nilius, Zhiming Zhu

Journal, date & volume: J Mol Cell Biol, 2012 Apr , 4, 88-96

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22241835

Abstract
Brown adipose tissue (BAT) is an energy-expending organ that produces heat. Expansion or activation of BAT prevents obesity and diabetes. Chronic cold exposure enhances thermogenesis in BAT through uncoupling protein 1 (UCP1) activation triggered via a β-adrenergic pathway. Here, we report that the cold-sensing transient receptor potential melastatin 8 (TRPM8) is functionally present in mouse BAT. Challenging brown adipocytes with menthol, a TRPM8 agonist, up-regulates UCP1 expression and requires protein kinase A activation. Upon mimicking long-term cold exposure with chronic dietary menthol application, menthol significantly increased the core temperatures and locomotor activity in wild-type mice; these effects were absent in both TRPM8(-/-) and UCP1(-/-) mice. Dietary obesity and glucose abnormalities were also prevented by menthol treatment. Our results reveal a previously unrecognized role for TRPM8, suggesting that stimulation of this channel mediates BAT thermogenesis, which could constitute a promising way to treat obesity.