Leptin receptor neurons in the dorsomedial hypothalamus regulate diurnal patterns of feeding, locomotion, and metabolism

The brain plays an essential role in driving daily rhythms of behavior and metabolism in harmony with environmental light–dark cycles. Within the brain, the dorsomedial hypothalamic nucleus (DMH) has been implicated in the integrative circadian control of feeding and energy homeostasis, but the underlying cell types are unknown. Here, we identify a role for DMH leptin receptor-expressing (DMH(LepR)) neurons in this integrative control. Using a viral approach, we show that silencing neurotransmission in DMH(LepR) neurons in adult mice not only increases body weight and adiposity but also phase-advances diurnal rhythms of feeding and metabolism into the light cycle and abolishes the normal increase in dark-cycle locomotor activity characteristic of nocturnal rodents. Finally, DMH(LepR)-silenced mice fail to entrain to a restrictive change in food availability. Together, these findings identify DMH(LepR) neurons as critical determinants of the daily time of feeding and associated metabolic rhythms.