Transcriptional control in brown and beige adipocytes

 描述（申请人提供）：能量平衡是生物体内能量的生物稳态，意味着从食物中摄入的能量等于能量消耗。当能量摄入超过能量消耗时，多余的能量将以脂肪的形式储存在脂肪和其他代谢组织中，最终导致肥胖并进一步发展为II型糖尿病。适应性产热是机体总能量消耗的主要组成部分之一，是指机体对环境温度或饮食变化的反应性产热。棕色脂肪组织是适应性产热耗散能量的主要场所。最近的研究表明，棕色和棕色样脂肪（米色脂肪）存在于成年人，其活动与体重指数呈负相关。冷暴露和循环激素都可以激活交感神经系统，对棕色和米色脂肪产生急性和慢性影响，但分子机制仍然知之甚少。这项格兰特提案旨在阐明棕色和米色脂肪中分子开关的功能，以控制能量消耗。在这个提议中，这个开关的生理作用 将使用细胞和小鼠模型进行研究。冷暴露和激素打开这个开关的方式以及棕色和米色脂肪中随后的分子事件将被研究。如何失调，这种开关有助于代谢紊乱也将探讨。因此，在人体中靶向这种分子开关可能为治疗肥胖和II型糖尿病提供新的疗法。

 DESCRIPTION (provided by applicant: Energy balance is the biological homeostasis of energy in living organisms, which means energy intake from food equals energy expenditure. When energy intake exceeds energy expenditure, excess energy will be stored as fat in adipose and other metabolic tissues, eventually leading to obesity and further development into type II diabetes. Adaptive thermogenesis represents one principle component of total energy expenditure, which refers to body heat production in response to changes of environmental temperature or diet. Brown adipose tissue is the major site of adaptive thermogenesis to dissipate energy. Recent studies indicate that brown and brown like fat (beige fat) are present in adult human, and their activities are inversely correlated with body mass index. Both cold exposure and circulating hormones can activate sympathetic nervous system to have acute and chronic impacts on brown and beige fat, although the molecular mechanisms still remain poorly understood. This Grant proposal aims to elucidate the function of a molecular switch in brown and beige fat to govern energy expenditure. In this proposal, the physiological role of this switch will be investigated using cellular and mouse models. The way that cold exposure and hormones turn on this switch and the molecular events afterwards in brown and beige fat will be studied. How dysregulation of this switch contributes to metabolic disorders will also be explored. Therefore, targeting this molecular switch in human may provide new therapies to treat obesity and type II diabetes.