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首页> 外文期刊>The journal of clinical investigation >FGF21 is an endocrine signal of protein restriction
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FGF21 is an endocrine signal of protein restriction

机译：FGF21是蛋白质限制的内分泌信号

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Enhanced fibroblast growth factor 21 (FGF21) production and circulation has been linkedto the metabolic adaptation to starvation. Here, we demonstrated that hepatic FGF21expression 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. Inthese animals, liver Fgf21 expression was increased within 24 hours ofreduced protein intake. In humans, circulating FGF21 levels increased dramaticallyfollowing 28 days on a LP diet. LP-induced increases in FGF21 were associated withincreased phosphorylation of eukaryotic initiation factor 2α (eIF2α) in theliver, and both baseline and LP-induced serum FGF21 levels were reduced in mice lackingthe eIF2α kinase general control nonderepressible 2 (GCN2). Finally, while proteinrestriction 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 andother data demonstrate that reduced protein intake underlies the increase in circulatingFGF21 in response to starvation and a ketogenic diet and that FGF21 is required forbehavioral and metabolic responses to protein restriction. FGF21 therefore represents anendocrine signal of protein restriction, which acts to coordinate metabolism and growthduring periods of reduced protein intake.
机译：增强的成纤维细胞生长因子21（FGF21）的生产和循环已被链接到饥饿的代谢适应。在这里，我们证明了饮食中的蛋白质限制而非能量限制诱导了肝FGF21的表达。在低蛋白质（LP）饮食的小鼠和大鼠中，循环中的FGF21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，LP饮食中的28天后，循环中的FGF21水平急剧增加。 LP诱导的FGF21的增加与肝脏中真核生物起始因子2α（eIF2α）磷酸化的增加相关，并且在缺乏eIF2α激酶一般控制不可抑制2（GCN2）的小鼠中，基线和LP诱导的血清FGF21水平均降低。最后，尽管蛋白质限制改变了野生型小鼠的食物摄入，能量消耗和体重增加，但缺乏FGF21的动物对LP饮食没有表现出这些变化。这些和其他数据表明，减少蛋白质的摄入量是对饥饿和生酮饮食的反应中循环FGF21含量增加的基础，并且对蛋白质限制的行为和代谢反应需要FGF21。因此，FGF21代表蛋白质限制的内分泌信号，其在减少蛋白质摄入的期间协调新陈代谢和生长。

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