Secretin-Activated Brown Fat Mediates Prandial Thermogenesis to Induce Satiation
Secretin-Activated Brown Fat Mediates Prandial Thermogenesis to Induce Satiation
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DOI：
10.1016/j.cell.2018.10.016
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发表时间：
2018-11-29
期刊：
影响因子：
64.5
通讯作者：
Klingenspor, Martin
中科院分区：
文献类型：
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作者：
Li, Yongguo;Schnabl, Katharina;Klingenspor, Martin
膳食相关的棕色脂肪（BAT）产热的分子介质和功能意义仍然难以捉摸。在这里，我们确定了肠道激素分泌素作为一种非交感神经BAT激活剂介导的膳食产热，从而诱导饱食，从而建立一个肠道分泌素-BAT-脑轴在哺乳动物的生理作用的膳食产热控制饱食。从机制上讲，膳食相关的循环促胰液素升高通过在与棕色脂肪细胞中的促胰液素受体结合后刺激脂解来激活BAT产热，在大脑中被感知并促进饱食。慢性输注修饰的人促胰液素可短暂提高饮食诱导的肥胖小鼠的能量消耗。人类受试者的临床试验表明，单餐摄入后的产热与餐后分泌素水平相关，并且分泌素输注增加BAT中的葡萄糖摄取。总的来说，我们的研究结果突出了BAT在控制饱腹感方面的功能，并使BAT成为治疗肥胖的更具吸引力的目标。
The molecular mediator and functional significance of meal-assosiated brown fat (BAT) thermogenesis remains elusive. Here, we identified the gut hormone secretin as a non-synmpathetic BAT activator mediating prandial thermogenesis, which consequentially induces satiation, thereby establishing a gut-secretin-BAT-brain axis in mammals with a physiological role of prandial thermogenesis in the control of satiation. Mechanistically, meal-associated rise in circulating secretin activates BAT thermogenesis by stimulating lipolysis upon binding to secretin receptors in brown adipocytes, is sensed in the brain and promotes satiation. Chronic infusion of a modified human secretin transiently elevates energy expenditure in diet-induced obese mice. Clinical trials with human subjects showed that thermogenesis after a single-meal ingestion correlated with postprandial secretin levels and that secretin infusions increased glucose uptake in BAT. Collectively, our findings highlight the largely unappreciated function of BAT in the control of satiation and qualify BAT as an even more attractive target for treating obesity.