title: Activation of the cold-sensing TRPM8 channel triggers UCP1-dependent thermogenesis and prevents obesity.
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.
authors.affiliation: Center for Hypertension and Metabolic Diseases, Department of Hypertension and Endocrinology,  Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042,  China.
authors.forename: Shuangtao
authors.initials: S
authors.lastname: Ma
authors.forename: Hao
authors.initials: H
authors.lastname: Yu
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhao
authors.forename: Zhidan
authors.initials: Z
authors.lastname: Luo
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Yinxing
authors.initials: Y
authors.lastname: Ni
authors.forename: Rongbing
authors.initials: R
authors.lastname: Jin
authors.forename: Liqun
authors.initials: L
authors.lastname: Ma
authors.forename: Peijian
authors.initials: P
authors.lastname: Wang
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Zhu
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Zhong
authors.forename: Daoyan
authors.initials: D
authors.lastname: Liu
authors.forename: Bernd
authors.initials: B
authors.lastname: Nilius
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Zhu
mesh_terms: D000818:Animals; D003080:Cold Temperature; D005260:Female; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control*; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*; D022722:Thermogenesis; D013697:Thermosensing; D000071256:Uncoupling Protein 1
chemical_list: D007473:Ion Channels; D024101:Mitochondrial Proteins; D050053:TRPM Cation Channels; C492297:TRPM8 protein, mouse; C000604371:UCP1 protein, human; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1