Leptin-receptor neurons in the dorsomedial hypothalamus regulate the timing of circadian rhythms in feeding and metabolism in mice

Animal behavior and metabolism are tightly coordinated with sleep-wake cycles governed by the brain in harmony with environmental light:dark cycles. Within the brain, the dorsomedial hypothalamic nucleus (DMH) has been implicated in the integrative control of feeding, energy homeostasis, and circadian rhythms [1], but the underlying cell types are unknown. Here, we identify a role for DMH leptin receptor-expressing neurons (DMH LepR ) in these effects. Using a viral approach, we show that silencing DMH LepR neurons in adult mice not only increases body weight and adiposity, but also shifts circadian rhythms in feeding and metabolism into the light-cycle. Moreover, DMH LepR silencing abolishes the normal increase in dark-cycle locomotor activity characteristic of nocturnal rodents. Furthermore, 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.