Endocrine regulation of the fasting response by PPARα-mediated induction of fibroblast growth factor 21
Endocrine regulation of the fasting response by PPARα-mediated induction of fibroblast growth factor 21
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DOI：
10.1016/j.cmet.2007.05.003
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发表时间：
2007-06-01
期刊：
影响因子：
29
通讯作者：
Kliewer, Steven A.
中科院分区：
文献类型：
--
作者：
Inagaki, Takeshi;Dutchak, Paul;Kliewer, Steven A.
过氧化物酶体增殖物激活的受体A（PPARα）调节饥饿期间脂肪作为能源的利用，并且是纤维化血脂异常药物的分子靶标。在这里，我们将内分泌激素成纤维细胞生长因子21（FGF21）确定为PPARA多效性作用的介体。 FGF21响应禁食和PPARA激动剂而直接由PPARα在肝脏中直接诱导。 FGF21反过来刺激白色脂肪组织中的脂解和肝脏中的酮症发生。 FGF21还减少了体育活动，并促进了Torpor，这是一种节省能量的短期冬眠状状态。这些发现表明，IPPAR Alpha-FGF21内分泌信号传导途径在调节对饥饿的自适应反应的各种代谢和行为方面中的意外作用。
Peroxisome proliferator-activated receptor a (PPAR alpha) regulates the utilization of fat as an energy source during starvation and is the molecular target for the fibrate dyslipidemia drugs. Here, we identify the endocrine hormone fibroblast growth factor 21 (FGF21) as a mediator of the pleiotropic actions of PPARa. FGF21 is induced directly by PPAR alpha in liver in response to fasting and PPARa agonists. FGF21 in turn stimulates lipolysis in white adipose tissue and ketogenesis in liver. FGF21 also reduces physical activity and promotes torpor, a short-term hibernation-like state of regulated hypothermia that conserves energy. These findings demonstrate an unexpected role for the IPPAR alpha-FGF21 endocrine signaling pathway in regulating diverse metabolic and behavioral aspects of the adaptive response to starvation.