Activation of the cold-sensing TRPM8 channel triggers UCP1-dependent thermogenesis and prevents obesity
Activation of the cold-sensing TRPM8 channel triggers UCP1-dependent thermogenesis and prevents obesity
复制标题
DOI：
10.1093/jmcb/mjs001
复制
发表时间：
2012-04-01
影响因子：
5.5
通讯作者：
Zhu, Zhiming
中科院分区：
文献类型：
--
作者：
Ma, Shuangtao;Yu, Hao;Zhu, Zhiming
棕色脂肪组织(BAT)是一种产生热量的能量消耗器官。BAT的扩张或激活可以预防肥胖和糖尿病。慢性冷暴露通过α-肾上腺素能途径激活解偶联蛋白1(UCP1)来促进蝙蝠产热。在这里，我们报告了在小鼠蝙蝠中存在冷感觉瞬时受体潜能Melastatin 8(TRPM8)的功能。用TRPM8激动剂薄荷醇攻击棕色脂肪细胞，上调UCP1的表达，并需要蛋白激酶A的激活。在模拟长期冷暴露和长期饮食薄荷醇应用后，薄荷醇显著增加了野生型小鼠的核心温度和运动活动；这些影响在TRPM8(/)和UCP1(/)小鼠中都没有。薄荷醇治疗也可以预防饮食肥胖和血糖异常。我们的结果揭示了TRPM8以前未知的作用，表明刺激这一通道介导了BAT的产热，这可能构成一种有希望的治疗肥胖症的方法。
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.