Leptin-induced thermogenesis in the circadian regulation of food intake

许多新陈代谢过程在一天中表现出周期性的调节，由一种被称为生物钟的内源性计时系统控制。代谢状态通过内分泌和自主神经信号传递到大脑，通过中枢调节回路调节食欲和能量消耗。一种重要的激素代谢信使是脂肪因子瘦素。瘦素缺乏会导致暴饮暴食，在肥胖者中观察到瘦素不敏感--同时，餐后产热反应迟钝。在这个项目中，我们研究了瘦素在餐后产热相关饱腹感调节的昼夜节律中的作用。我们使用具有瘦素突变和组织特异性瘦素受体缺失的小鼠来验证这样的假设，即高能量饮食的摄入量受到瘦素诱导的产热的昼夜节律门控的调节。在肥胖等情况下，不当的食物摄入或瘦素抵抗可能会导致日常饮食模式的中断，从而促进代谢紊乱的发展。

Many metabolic processes show cyclic regulation across the day controlled by an endogenous timekeeping system termed the circadian clock. Metabolic state is transmitted to the brain via endocrine and autonomic signals to adapt appetite and energy expenditure through central regulatory circuits. One important hormonal metabolic messenger is the adipokine leptin. Leptin deficiency promotes overeating and leptin insensitivity is observed in obese individuals – in parallel to a blunting in postprandial thermogenesis responses. In this project, we study the role of leptin in the circadian control of postprandial thermogenesis-associated satiety regulation. We use mice with mutations in leptin and tissue-specific leptin receptor deletion to test the hypothesis that high-energy diet intake is regulated by a circadian gating of leptin-induced thermogenesis. Under conditions such as obesity, mistimed food intake or leptin resistance may lead to a disruption of diurnal eating patterns, thus promoting the development of metabolic disorders.