FGF21 is an endocrine signal of protein restriction
FGF21 is an endocrine signal of protein restriction
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DOI：
10.1172/jci74915
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发表时间：
2014-09-01
影响因子：
15.9
通讯作者：
Morrison, Christopher D.
中科院分区：
文献类型：
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作者：
Laeger, Thomas;Henagan, Tara M.;Morrison, Christopher D.
增强的成纤维细胞生长因子21（FGF21）的产生和循环与对饥饿的代谢适应有关。在这里，我们证明了肝脏FGF21的表达是由饮食蛋白质限制诱导的，而不是能量限制。在喂食低蛋白（LP）饮食的小鼠和大鼠中，循环FGF 21增加了10倍。在这些动物中，肝脏Fgf21表达在蛋白质摄入减少的24小时内增加。在人类中，循环FGF 21水平在LP饮食28天后急剧增加。脂蛋白诱导的FGF21增加与肝脏中真核起始因子2 α（eIF2 α）磷酸化增加相关，在缺乏eIF2 α激酶一般对照非去抑制因子2（GCN 2）的小鼠中，基线和脂蛋白诱导的血清FGF21水平均降低。最后，虽然蛋白质限制改变了WT小鼠的食物摄入量，能量消耗和体重增加，但FGF21缺陷动物在LP饮食中没有表现出这些变化。这些和其他数据表明，蛋白质摄入量减少是响应饥饿和生酮饮食的循环FGF 21增加的基础，并且FGF 21是对蛋白质限制的行为和代谢反应所必需的。因此，FGF21代表蛋白质限制的内分泌信号，其在蛋白质摄入减少期间起协调代谢和生长的作用。
Enhanced fibroblast growth factor 21 (FGF21) production and circulation has been linked to the metabolic adaptation to starvation. Here, we demonstrated that hepatic FGF21 expression is induced by dietary protein restriction, but not energy restriction. Circulating FGF21 was increased 10-fold in mice and rats fed a low-protein (LP) diet. In these animals, liver Fgf21 expression was increased within 24 hours of reduced protein intake. In humans, circulating FGF21 levels increased dramatically following 28 days on a LP diet. LP-induced increases in FGF21 were associated with increased phosphorylation of eukaryotic initiation factor 2 alpha (eIF2 alpha) in the liver, and both baseline and LP-induced serum FGF21 levels were reduced in mice lacking the eIF2 alpha kinase general control nonderepressible 2 (GCN2). Finally, while protein restriction altered food intake, energy expenditure, and body weight gain in WT mice, FGF21-deficient animals did not exhibit these changes in response to a LP diet. These and other data demonstrate that reduced protein intake underlies the increase in circulating FGF21 in response to starvation and a ketogenic diet and that FGF21 is required for behavioral and metabolic responses to protein restriction. FGF21 therefore represents an endocrine signal of protein restriction, which acts to coordinate metabolism and growth during periods of reduced protein intake.