过氧化物酶体增殖物激活受体α介导的成纤维细胞生长因子21诱导对禁食反应的内分泌调节。

Endocrine regulation of the fasting response by PPARalpha-mediated induction of fibroblast growth factor 21.

作者信息

Inagaki Takeshi, Dutchak Paul, Zhao Guixiang, Ding Xunshan, Gautron Laurent, Parameswara Vinay, Li Yong, Goetz Regina, Mohammadi Moosa, Esser Victoria, Elmquist Joel K, Gerard Robert D, Burgess Shawn C, Hammer Robert E, Mangelsdorf David J, Kliewer Steven A

机构信息

Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

出版信息

Cell Metab. 2007 Jun;5(6):415-25. doi: 10.1016/j.cmet.2007.05.003.

DOI:10.1016/j.cmet.2007.05.003

PMID:17550777

Abstract

Peroxisome proliferator-activated receptor alpha (PPARalpha) 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 PPARalpha. FGF21 is induced directly by PPARalpha in liver in response to fasting and PPARalpha 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 PPARalpha-FGF21 endocrine signaling pathway in regulating diverse metabolic and behavioral aspects of the adaptive response to starvation.

摘要

过氧化物酶体增殖物激活受体α（PPARα）在饥饿期间调节脂肪作为能量来源的利用，并且是贝特类血脂异常药物的分子靶点。在此，我们确定内分泌激素成纤维细胞生长因子21（FGF21）是PPARα多效性作用的介质。FGF21在肝脏中由PPARα直接诱导，以响应禁食和PPARα激动剂。FGF21继而刺激白色脂肪组织中的脂肪分解和肝脏中的生酮作用。FGF21还会降低身体活动并促进蛰伏，蛰伏是一种类似短期冬眠的调节性体温过低状态，可保存能量。这些发现证明了PPARα - FGF21内分泌信号通路在调节对饥饿的适应性反应的各种代谢和行为方面具有意想不到的作用。