Hypothalmic Circuits Regulating Energy Balance and Obesity: Synaptic Physiology

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Project Summary According to the CDC more that 35% of U.S. adults and 20% of U.S. children are obese and therefore are at risk of life-threatening diseases including diabetes, stroke, heart disease and cancers. Further, obesity has huge economic consequences in medical care and lost wages. Studies on obesity clearly indicate important roles for hypothalamic POMC neurons in regulating aspects of energy homeostasis. These neurons have been traditionally considered to respond to post-prandial cues and maintain energy balance over protracted timescales. However, recent work from our lab and others indicate that these neurons release many transmitters and can respond and act more quickly than previously appreciated. The overall goals of this proposal are to determine how food intake and activation of these neurons changes the short-term response to food intake and alters food intake at the next meal. Specifically, we aim to learn how eating patterns might play into energy balance regulation as this is something people could readily optimize with the appropriate knowledge. We will determine the frequency with which POMC neurons can be stimulated to best reduce food intake and will determine how the activity of POMC neurons is regulated in a meal-to-meal fashion. Since POMC neuron activation usually leads to the reduction of food intake or termination of a meal, we will examine the timing between meals that yields the smallest meal size for a subsequent meal. Ultimately, the studies stand to provide mechanistic insight into the reported efficacy of intermittent fasting and may provide insight into the most beneficial timing of meals for weight loss.