共 21 条
Activation of the cold-sensing TRPM8 channel triggers UCP1-dependent thermogenesis and prevents obesity
被引：177
|作者：
Ma, Shuangtao
[1
]
Yu, Hao
[1
]
Zhao, Zhigang
[1
]
Luo, Zhidan
[1
]
Chen, Jing
[1
]
Ni, Yinxing
[1
]
Jin, Rongbing
[1
]
Ma, Liqun
[1
]
Wang, Peijian
[1
]
Zhu, Zhenyu
[1
]
Li, Li
[1
]
Zhong, Jian
[1
]
Liu, Daoyan
[1
]
Nilius, Bernd
[2
]
Zhu, Zhiming
[1
]
机构：
[1] Third Mil Med Univ, Chongqing Inst Hypertens, Ctr Hypertens & Metab Dis, Dept Hypertens & Endocrinol,Daping Hosp, Chongqing 400042, Peoples R China
[2] Katholieke Univ Leuven, Dept Mol Cell Biol, Lab Ion Channel Res, Louvain, Belgium
基金：
中国国家自然科学基金;
关键词：
TRPM8;
uncoupling protein 1;
menthol;
thermogenesis;
brown adipose tissue;
obesity;
BROWN ADIPOSE-TISSUE;
ADAPTIVE THERMOGENESIS;
THYROID-HORMONE;
FATTY-ACIDS;
UCP1;
MICE;
TEMPERATURE;
MENTHOL;
PROTEIN;
IDENTIFICATION;
D O I：
10.1093/jmcb/mjs001
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ;
090102 ;
摘要：
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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页码：88 / 96
页数：9
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