Hypothalmic Circuits Regulating Energy Balance and Obesity: Synaptic Physiology

项目摘要 根据疾病预防控制中心的数据，35%的美国成年人和20%的美国儿童患有肥胖症， 糖尿病、中风、心脏病和癌症等危及生命的疾病的风险。此外，肥胖症 在医疗保健和工资损失方面造成了巨大的经济后果。对肥胖症的研究清楚地表明， 下丘脑POMC神经元在调节能量稳态方面的作用。这些神经元 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，我们实验室和其他人最近的工作表明，这些神经元释放许多 发射机，并可以响应和行动比以前更快地认识到。本项目的总体目标 他们的建议是确定食物摄入和这些神经元的激活如何改变对食物的短期反应。 食物摄入量，并改变下一餐的食物摄入量。具体来说，我们的目标是了解饮食模式如何发挥作用， 能量平衡调节，因为这是人们可以很容易地优化适当的 知识我们将确定POMC神经元可以被刺激以最好地减少食物的频率。 摄入量，并将决定POMC神经元的活动是如何在一顿饭到一顿饭的方式进行调节。以来 POMC神经元激活通常导致食物摄入减少或停止进餐，我们将研究 两餐之间的时间安排，为下一餐提供最小的膳食量。最终，研究 站在提供机制洞察报告的间歇性禁食的疗效，并可能提供洞察力 最有利于减肥的饮食时间

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.