Leptin-induced thermogenesis in the circadian regulation of food intake

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.