Fibroblast growth factor 21: from pharmacology to physiology
Fibroblast growth factor 21: from pharmacology to physiology
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DOI：
10.3945/ajcn.2009.28449b
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发表时间：
2010-01-01
影响因子：
7.1
通讯作者：
Mangelsdorf, David J.
中科院分区：
文献类型：
--
作者：
Kliewer, Steven A.;Mangelsdorf, David J.
成纤维细胞生长因子21（FGF 21）是FGF家族的非典型成员，其作为内分泌激素起作用。药理学研究表明，FGF 21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引起体重减轻。在瘦啮齿类动物中，通过涉及核受体过氧化物酶体增殖物激活受体α的机制，通过长期禁食强烈诱导肝脏中的FGF 21表达。FGF 21又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1 α，并刺激肝细胞增生、脂肪酸氧化和生酮。FGF 21还阻断了体细胞生长，并使小鼠对冬眠样的麻木状态敏感。因此，FGF 21在引发和协调适应性饥饿反应中起关键作用。有趣的是，FGF 21的表达在白色脂肪组织中由过氧化物酶体增殖物激活受体γ诱导，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FGF 21的药理学和生理学作用的理解的最新进展。美国临床营养杂志2010;91（增刊）：254 S-7S。
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 1 alpha 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. Am J Clin Nutr 2010;91(suppl):254S-7S.