Delineation of the role of brainstem pro-opiomelanocorin neurons in energy balance

肥胖和2型糖尿病代表了21世纪世纪的主要医学和经济挑战。了解调节食物消耗的生物学机制对于成功治疗和预防肥胖和2型糖尿病至关重要。大脑代表着能量平衡的主要协调者，它使用许多交织的神经回路来不断评估和应对营养状态的变化。大脑黑素皮质素网络是能量稳态的基本调节器，并且充当许多这些信号的网关。因此，阿黑皮素原（POMC）调节食欲，食物偏好，体重和血糖的确切机制的明确理解是强烈的兴趣。本申请的目的是确定负责传递能量平衡信息的特定POMC神经元，并通过最先进的药物遗传学和遗传技术证明其操纵与代谢适应性直接相关。我们还将研究饮食和肥胖对POMC能量平衡回路功能的影响。通过识别大脑中调节能量平衡的主要关键细胞，我们预计这些数据最终将对全球代谢疾病的治疗产生转化效益。

Obesity and type 2 diabetes represent major medical and economic challenges of the 21st century. An understanding of the biological mechanisms regulating food consumption is essential to both the successful treatment and prevention of obesity and type 2 diabetes. The brain represents the master co-coordinator of energy balance, employing a number of interwoven neurological circuits to continually appraise and respond to changes in nutritional state. The brain melanocortin network is a fundamental regulator of energy homeostasis and serves as a gateway for many of these signals. Therefore, a clear understanding of the precise mechanism through which pro-opiomelanocortin (POMC) modulates appetite, food preference, body weight, and blood glucose is of intense interest. The aim of this application is to identify specific POMC neurons responsible for communicating energy balance information and to demonstrate that their manipulation, through state of the art pharmacogenetic and genetic techniques, is of direct relevance to metabolic fitness. We will also examine the impact of diet and adiposity on POMC energy balance circuitry function. Through the identification of primary, critical cells in the brain regulating energy balance, we anticipate that these data will ultimately have translational benefit for the treatment of global metabolic disease.