FGF21 Signals Protein Status to the Brain and Adaptively Regulates Food Choice and Metabolism
FGF21 Signals Protein Status to the Brain and Adaptively Regulates Food Choice and Metabolism
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DOI：
10.1016/j.celrep.2019.05.022
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发表时间：
2019-06-04
期刊：
影响因子：
8.8
通讯作者：
Morrison, Christopher D.
中科院分区：
文献类型：
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作者：
Hill, Cristal M.;Laeger, Thomas;Morrison, Christopher D.
减少饮食蛋白质摄入量会导致大量营养素偏好、能量消耗、生长和葡萄糖稳态的适应性生理变化。我们证明，从大脑中删除FGF21共同受体βKlotho(KLB)会导致小鼠无法对蛋白质限制做出生理反应，这种影响可以通过全身删除FGF21来复制。被迫食用低蛋白饮食的小鼠表现出生长减慢、能量消耗增加以及对饮食诱导的肥胖的抵抗力，但大脑中FGF21信号的丢失完全消除了这种反应。当给予高蛋白替代品时，蛋白质限制的小鼠表现出转向含蛋白质的食物，而中枢FGF21信号对这种反应是必不可少的。FGF21是连接肝脏和大脑的内分泌信号，在蛋白质限制期间调节代谢和摄食行为的适应性、动态平衡变化。
Reduced dietary protein intake induces adaptive physiological changes in macronutrient preference, energy expenditure, growth, and glucose homeostasis. We demonstrate that deletion of the FGF21 co-receptor beta Klotho (Klb) from the brain produces mice that are unable to mount a physiological response to protein restriction, an effect that is replicated by whole-body deletion of FGF21. Mice forced to consume a low-protein diet exhibit reduced growth, increased energy expenditure, and a resistance to diet-induced obesity, but the loss of FGF21 signaling in the brain completely abrogates that response. When given access to a higher protein alternative, protein-restricted mice exhibit a shift toward protein-containing foods, and central FGF21 signaling is essential for that response. FGF21 is an endocrine signal linking the liver and brain, which regulates adaptive, homeostatic changes in metabolism and feeding behavior during protein restriction.