Hypothalmic Circuits Regulating Energy Balance and Obesity: Synaptic Physiology

项目摘要 根据疾控中心的数据，超过35%的美国成年人和20%的美国儿童患有肥胖症，因此 糖尿病、中风、心脏病和癌症等威胁生命的疾病的风险。此外，肥胖症已经 医疗保健和工资损失的巨大经济后果。关于肥胖的研究清楚地表明 下丘脑POMC神经元在能量平衡调节方面的作用。这些神经元一直是 传统上被认为是对餐后暗示的反应，并在长时间内保持能量平衡 时间尺度。然而，我们实验室和其他实验室最近的研究表明，这些神经元释放了许多 发射器，并可以更快地响应和行动，比以前所认识到的。这个项目的总体目标是 是为了确定这些神经元的食物摄取和激活如何改变对 食物摄入量和改变下一餐的食物摄入量。具体地说，我们的目标是了解饮食模式可能起到的作用 能量平衡调节，因为这是人们可以很容易地用适当的 知识。我们将确定刺激POMC神经元以最好地减少食物摄入的频率 并将决定POMC神经元的活动如何以餐与餐之间的方式进行调节。自.以来 POMC神经元的激活通常会导致食物摄入量的减少或一顿饭的终止，我们将研究 两餐之间的时间间隔，为随后的一餐产生最小的一餐。最终，这些研究 提供对间歇性禁食的报道的有效性的机械性见解，并可能提供见解 成为减肥最有益的进餐时间。

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.