Leptin-induced thermogenesis in the circadian regulation of food intake

许多代谢过程在一天中表现出循环调节，由一种称为昼夜节律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。一个重要的激素代谢信使是脂肪因子瘦素。瘦素缺乏会促进暴饮暴食，在肥胖个体中观察到瘦素不敏感——与餐后产热反应的钝化同时发生。在这个项目中，我们研究瘦素在餐后产热相关饱腹感调节的昼夜节律控制中的作用。我们使用瘦素突变和组织特异性瘦素受体缺失的小鼠来验证高能饮食摄入是由瘦素诱导的昼夜节律门控调节的假设。在肥胖等情况下，不合时宜的食物摄入或瘦素抵抗可能导致昼夜饮食模式的破坏，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.