Neural circuits coordinating protein intake: Role of FGF21

项目摘要 生存取决于在生理和行为上适应不断变化的营养环境， 在哺乳动物中，这种体内平衡主要是由作用于大脑的营养激素介导的。最近 几十年来，我们在理解调节能量的神经机制方面取得了实质性进展。 摄入量和总食物摄入量，但动物如何感知个体大量营养素并在它们之间进行自我选择 仍然定义不清。我们的实验室最近发现，肝源性激素FGF21在大脑中起作用， 作为蛋白质状态的信号。而正常小鼠适应性地“感知”蛋白质限制并改变食物摄入量， 为了特异性地寻找和消耗蛋白质，这种反应在缺乏FGF21或脑FGF21的小鼠中丧失。 信号该项目将定义介导FGF21依赖性变化的大脑区域和神经表型 在进食行为，并在这样做将提供第一个深入了解神经生物学管理宏量营养素 选择尽管饮食结构和食物选择对健康的重要性， 虽然我们不知道改变饮食习惯的建议，但我们对大脑如何控制膳食宏量营养素几乎一无所知。 选择因此，在本申请中提出的工作将通过严格地探测在本领域中的应用而显著地影响本领域。 控制进食行为的新机制。

Project Summary Survival is contingent upon physiologically and behaviorally adapting to a changing nutritional environment, and in mammals this homeostasis is largely mediated by nutritional hormones acting in the brain. Recent decades have seen substantial progress in our understanding of the neural mechanisms mediating energy intake and total food intake, but how animals sense individual macronutrients and self-select between them remains poorly defined. Our lab has recently discovered that the liver-derived hormone FGF21 acts in the brain as a signal of protein status. While normal mice adaptively ‘sense’ protein restriction and alter food intake in order to specifically seek and consume protein, this response is lost in mice lacking FGF21 or brain FGF21 signaling. The project will define the brain areas and neural phenotypes mediating FGF21-dependent changes in feeding behavior, and in doing so will provide the first insight into the neurobiology governing macronutrient choice. Despite the importance of dietary composition and food choice to health, and despite persistent dietary advice to change eating habits, we know almost nothing about how the brain controls dietary macronutrient choice. Thus the work proposed in this application will substantially impact the field by rigorously probing the novel mechanisms controlling feeding behavior.