期刊
JOURNAL OF MOLECULAR CELL BIOLOGY
卷 4, 期 2, 页码 88-96出版社
OXFORD UNIV PRESS
DOI: 10.1093/jmcb/mjs001
关键词
TRPM8; uncoupling protein 1; menthol; thermogenesis; brown adipose tissue; obesity
类别
资金
- National Basic Research Program of China [2012CB517805, 2012CB517806]
- National Natural Science Foundation of China [30890042]
- Ministry of Education in China
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 -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.
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