Neural circuits coordinating protein intake: Role of FGF21

项目摘要 生存取决于生理和行为对不断变化的营养环境的适应， 在哺乳动物中，这种动态平衡在很大程度上是由作用于大脑的营养荷尔蒙调节的。近期 几十年来，我们对调节能量的神经机制的理解取得了实质性的进展 摄入量和总摄食量，但动物如何感觉到个别的常量营养素并在它们之间进行自我选择 仍然没有明确的定义。我们的实验室最近发现，肝脏衍生的激素FGF21在大脑中起作用 作为蛋白质状态的信号。而正常小鼠自适应地“感觉”蛋白质限制并改变食物摄入量 为了特定地寻找和消费蛋白质，这种反应在缺乏FGF21或大脑FGF21的小鼠中丢失 发信号。该项目将定义介导FGF21依赖变化的脑区和神经表型 在摄食行为方面，这样做将提供对支配大量营养素的神经生物学的第一次洞察 选择。尽管饮食结构和食物选择对健康很重要，而且尽管坚持饮食 关于改变饮食习惯的建议，我们对大脑如何控制饮食中的常量营养素几乎一无所知 选择。因此，本申请中提议的工作将通过严格探索 控制摄食行为的新机制。

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.