代谢综合征包括一系列与能量过剩相关的疾病，研究其发病机制，寻找新的治疗靶点，有着重要意义。生物节律紊乱在代谢综合征的发病中起着非常重要的作用，而高脂饮食是导致生物节律紊乱的重要因素。我们发现下丘脑视交叉上核PPARgamma的表达呈现出昼夜节律性，而在高脂饮食小鼠日间进食比显著升高，下丘脑PPARgamma表达降低，节律性消失。视交叉上核神经元特异性敲除PPARgamma小鼠出现黑暗环境下自主活动节律紊乱，PER1 表达节律紊乱。PPARgamma在中枢节律调控中是否起作用，尚未见报道。我们提出假说：视交叉上核PPARgamma在中枢节律调控中起着非常重要的作用，感知代谢物的变化，高脂饮食导致PPARgamma表达降低，节律性消失，动物自主活动和进食节律紊乱，肝脏代谢酶异常，导致代谢综合征的发生。我们将使用视交叉上核神经元特异性敲除PPARgamma小鼠，研究其在中枢节律中的作用。

Metabolic syndrome is associated with the risk of developing cardiovascular disease, type 2 diabetes and neurodegenerative disease. Recent research has shown that circadian desynchronization is associated with increase in metabolic risks favoring obesity and cardiovascular diseases. The circadian system is a complex feedback network that is closely linked to metabolic homeostasis and involves interactions between the central nervous system and peripheral tissues. Desynchronization between the central and peripheral clocks by altered timing of food intake and diet composition can lead to uncoupling of peripheral clocks from the central pacemaker and to the metabolic disorders. Metabolic dysfunction is associated with circadian disturbances at both central and peripheral levels and, eventual disruption of circadian clock functioning can lead to obesity. Therefore, it is important to study the mechanisms of circadian rhythm regulation and dysfunction. ..PPARgamma is a transcriptional factor whose agonists are widely used for type 2 diabetes, and protective for various neurodegenerative diseases. Varieties of studies have reported that PPARgamma as a peripheral factor participating in regulation of cardiovascular rhythms, liver rhythms, and adipocyte rhythms. However, the role of PPARgamma in central clock regulation has never been reported. Our preliminary data show that PPARgamma is expressed in the suprachiasmatic nucleus ( SCN) of hypothalamus in a circadian manner. Moreover, PPARgamma decreased with the high-fat diet feeding and the circadian manner disappeared. Moreover, mice with neuronal specific knockout of PPARgamma in SCN are incapable of maintaining normal circadian rhythms of activity behavior in darkness. 3 months later, the average weight of mice with neuronal specific knockout of PPARgamma in SCN are much higher than that of the control mice...Therefore, we hypothesize that the hypothalamic PPARgamma plays an important role in SCN circadian regulation and its dysfunction is involved in the development of metabolic syndrome. In this project, we will study the expression of PPARgamma in SCN, and the role of PPARgamma in hypothalamic circadian regulation and high-fat diet induced metabolic syndrome.