Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 73590-9041, USA.
Am J Clin Nutr. 2010 Jan;91(1):254S-257S. doi: 10.3945/ajcn.2009.28449B. Epub 2009 Nov 11.
Fibroblast growth factor 21 (FGF21) is an atypical member of the FGF family that functions as an endocrine hormone. Pharmacologic studies show that FGF21 has broad metabolic actions in obese rodents and primates that include enhancing insulin sensitivity, decreasing triglyceride concentrations, and causing weight loss. In lean rodents, FGF21 expression is strongly induced in liver by prolonged fasting through a mechanism that involves the nuclear receptor peroxisome proliferator-activated receptor alpha. FGF21, in turn, induces the transcriptional coactivator protein peroxisome proliferator-activated receptor gamma coactivator protein 1alpha and stimulates hepatic gluconeogenesis, fatty acid oxidation, and ketogenesis. FGF21 also blocks somatic growth and sensitizes mice to a hibernation-like state of torpor. Thus, FGF21 plays a key role in eliciting and coordinating the adaptive starvation response. Interestingly, FGF21 expression is induced in white adipose tissue by peroxisome proliferator-activated receptor gamma, which suggests that it also regulates metabolism in the fed state. This article highlights recent advances in our understanding of FGF21's pharmacologic and physiologic actions.
成纤维细胞生长因子 21（FGF21）是 FGF 家族中的一种非典型成员，作为一种内分泌激素发挥作用。药理研究表明，FGF21 在肥胖啮齿动物和灵长类动物中具有广泛的代谢作用，包括增强胰岛素敏感性、降低甘油三酯浓度和导致体重减轻。在瘦鼠中，FGF21 的表达通过涉及核受体过氧化物酶体增殖物激活受体α的机制，在长期禁食后在肝脏中被强烈诱导。反过来，FGF21 诱导转录共激活蛋白过氧化物酶体增殖物激活受体γ共激活蛋白 1α，并刺激肝糖异生、脂肪酸氧化和酮体生成。FGF21 还阻止躯体生长并使小鼠对类似于冬眠的状态敏感。因此，FGF21 在引发和协调适应性饥饿反应中起着关键作用。有趣的是，过氧化物酶体增殖物激活受体γ诱导白色脂肪组织中 FGF21 的表达，这表明它也调节进食状态下的代谢。本文重点介绍了我们对 FGF21 的药理和生理作用的理解的最新进展。
