生物谷報道：來自西南醫(yī)學中心的研究者稱,，一個關鍵的激素可以改變饑餓小鼠的代謝途徑，并且以類似冬眠的方式讓小鼠保存能量,。這個起著抗饑餓效果的激素，就是成纖維生長因子21（fibroblast growth factor 21；FGF21）,。此項研究發(fā)表在近日的Cell Metabolism雜志上，為治療人類肥胖癥,、代謝紊亂提供了一個潛在的藥物靶點
在饑餓小鼠中,，F(xiàn)GF21是受一個調(diào)控脂肪作為能量的細胞受體激活的。激活后,，F(xiàn)GF21可以將細胞的代謝途徑由原先的以碳水化合物為能量來源,，轉變成以脂肪為能量來源。不僅如此,，F(xiàn)GF21還誘導小鼠體溫及生理活性下降,，以一種近乎“冬眠”的方式幫助小鼠度過饑餓時光，存活下來,。
“這個激素可以在小鼠缺乏足夠營養(yǎng)的時候,，及時改變代謝、行為途徑,，”西南醫(yī)學中心的分子生物學和藥理學教授Steven Kliewer博士介紹說,，他是此項研究的主持者,，“我們希望能針對這條激素-受體信號通路，設計出攻克人類肥胖癥和其他病癥的新一代藥物,。”
原始出處:
Cell Metabolism, Vol 5, 415-425, 06 June 2007
Endocrine Regulation of the Fasting Response by PPARα-Mediated Induction of Fibroblast Growth Factor 21
Takeshi Inagaki,1 Paul Dutchak,1 Guixiang Zhao,1 Xunshan Ding,2,3 Laurent Gautron,2,4,5 Vinay Parameswara,4 Yong Li,8 Regina Goetz,9 Moosa Mohammadi,9 Victoria Esser,4 Joel K. Elmquist,2,4,5 Robert D. Gerard,1,4 Shawn C. Burgess,6 Robert E. Hammer,7 David J. Mangelsdorf,2,3 and Steven A. Kliewer1,2,
1 Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
2 Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
3 Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
4 Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
5 Division of Hypothalamic Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
6 Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
7 Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
8 Van Andel Research Institute, Grand Rapids, MI 49503, USA
9 Department of Pharmacology, New York University School of Medicine, New York, NY 10016, USA
Corresponding author
Steven A. Kliewer
[email protected]
Summary
Peroxisome proliferator-activated receptor α (PPARα) 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 PPARα. FGF21 is induced directly by PPARα in liver in response to fasting and PPARα 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 PPARα-FGF21 endocrine signaling pathway in regulating diverse metabolic and behavioral aspects of the adaptive response to starvation.
