FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis
FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis
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DOI：
10.1101/gad.177857.111
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发表时间：
2012-02-01
影响因子：
10.5
通讯作者：
Spiegelman, Bruce M.
中科院分区：
文献类型：
--
作者：
Fisher, Ffolliott M.;Kleiner, Sandra;Spiegelman, Bruce M.
某些白色脂肪组织（WAT）贮库在长时间的冷暴露或暴露于β-肾上腺素能化合物时能够容易地转化为“棕色样”状态。该过程的特征在于解偶联蛋白1（UCP 1）阳性多室脂肪细胞袋的出现，并用于增加生物体的产热能力。我们在这里表明，成纤维细胞生长因子21（FGF 21）发挥了生理作用，在这产热招募的水。事实上，缺乏FGF 21的小鼠表现出适应慢性冷暴露的能力受损，WAT的布朗宁减少。脂肪来源的FGF 21以自分泌/旁分泌方式起作用，以增加脂肪组织中UCP 1和其他产热基因的表达。FGF 21至少部分地通过独立于mRNA表达而增强脂肪组织PGC-1 α蛋白水平来调节这一过程。我们的结论是，FGF 21的行为，激活和扩大产热机制在体内提供了一个强大的防御体温过低。
Certain white adipose tissue (WAT) depots are readily able to convert to a "brown-like" state with prolonged cold exposure or exposure to beta-adrenergic compounds. This process is characterized by the appearance of pockets of uncoupling protein 1 (UCP1)-positive, multilocular adipocytes and serves to increase the thermogenic capacity of the organism. We show here that fibroblast growth factor 21 (FGF21) plays a physiologic role in this thermogenic recruitment of WATs. In fact, mice deficient in FGF21 display an impaired ability to adapt to chronic cold exposure, with diminished browning of WAT. Adipose-derived FGF21 acts in an autocrine/paracrine manner to increase expression of UCP1 and other thermogenic genes in fat tissues. FGF21 regulates this process, at least in part, by enhancing adipose tissue PGC-1 alpha protein levels independently of mRNA expression. We conclude that FGF21 acts to activate and expand the thermogenic machinery in vivo to provide a robust defense against hypothermia.