对饮食蛋白质限制的代谢反应需要增加成纤维细胞生长因子21（FGF21），而GCN2缺失会延迟这种增加。
Metabolic Responses to Dietary Protein Restriction Require an Increase in FGF21 that Is Delayed by the Absence of GCN2.
作者信息
Laeger Thomas, Albarado Diana C, Burke Susan J, Trosclair Lexus, Hedgepeth John W, Berthoud Hans-Rudolf, Gettys Thomas W, Collier J Jason, Münzberg Heike, Morrison Christopher D
机构信息
Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.
出版信息
Cell Rep. 2016 Jul 19;16(3):707-16. doi: 10.1016/j.celrep.2016.06.044. Epub 2016 Jul 7.
FGF21 contributes to the metabolic response to dietary protein restriction, and prior data implicate GCN2 as the amino acid sensor linking protein restriction to FGF21 induction. Here, we demonstrate the persistent and essential role of FGF21 in the metabolic response to protein restriction. We show that Fgf21 KO mice are fully resistant to low protein (LP)-induced changes in food intake, energy expenditure (EE), body weight gain, and metabolic gene expression for 6 months. Gcn2 KO mice recapitulate this phenotype, but LP-induced effects on food intake, EE, and body weight subsequently begin to appear after 14 days on diet. We show that this delayed emergence of LP-induced metabolic effects in Gcn2 KO mice coincides with a delayed but progressive increase of hepatic Fgf21 expression and blood FGF21 concentrations over time. These data indicate that FGF21 is essential for the metabolic response to protein restriction but that GCN2 is only transiently required for LP-induced FGF21.
成纤维细胞生长因子21（FGF21）有助于机体对饮食蛋白质限制产生代谢反应，先前的数据表明，一般控制非抑制性2（GCN2）作为将蛋白质限制与FGF21诱导联系起来的氨基酸传感器。在此，我们证明了FGF21在机体对蛋白质限制的代谢反应中具有持续且至关重要的作用。我们发现，Fgf21基因敲除（KO）小鼠在6个月内对低蛋白（LP）诱导的食物摄入量、能量消耗（EE）、体重增加及代谢基因表达变化完全具有抗性。Gcn2 KO小鼠重现了这一表型，但在饮食14天后LP诱导的对食物摄入量、EE及体重的影响随后开始显现。我们发现，Gcn2 KO小鼠中LP诱导的代谢效应延迟出现与肝脏Fgf21表达及血液FGF21浓度随时间延迟但逐渐增加相吻合。这些数据表明，FGF21对机体对蛋白质限制的代谢反应至关重要，但GCN2仅在LP诱导FGF21过程中短暂发挥作用。
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