Role of AMPK and mTOR in the hypothalamus and brainstem for the reduction of food intake by the amino acids leucine and serine

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The popularity of high protein diets for weight loss in society of Western civilization highlights the perception that dietary protein influences body weight, and underscores the need to study the mechanisms underlying this phenomenon. The current proposal seeks to clarify the biological basis whereby the brain controls feeding behavior in response to variations in protein balance. This work is especially important considering that protein balance takes priority over energy balance, and thus tapping into this regulatory system will reveal novel approaches to regulate food intake and treat obesity. Currently we have very little information regarding the mechanisms through which individual amino acids may act within the brain, or the potential interaction between various brain areas such as the hypothalamus and brainstem, two major centers of food intake regulation. It is well supported that leucine suppresses food intake when administered into the brain and serine is supposed to influence food intake. Therefore, the main objective of the present study is to investigate the role of the amino acid-sensing system mammalian target of rapamycin (mTOR) and the cellular energy-sensing enzyme AMP-activated protein kinase (AMPK) as downstream molecules that may act in concert or independently to mediate the effects of amino acids on food intake and neuropeptide gene expression. This research will use in vivo approaches to determine whether AMPK and/or mTOR are critical detectors of hypothalamic amino acids, particularly leucin and serine, and whether the brainstem contributes to the amino acid-dependent regulation of food intake. As such, the studies proposed in the current work are particularly novel, and could lay the foundation for new approaches to the regulation of food intake and treatment of obesity.