Neural circuits coordinating protein intake: Role of FGF21

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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.