Proopiomelanocortin (POMC) neurons in the arcuate nucleus of ventral hypothalamus and the nucleus tractus solitarius are involved in many biological functions. Nuclear receptor Nr1d1 and Nr1d2 are the key component of the molecular circadian clock machinery and are widely expressed in the brain. Here we address the role of Nr1d1/Nr1d2 in POMC neurons using conditional knockout mouse models. Mice with Nr1d1 and Nr1d2 specifically depleted in POMC neurons (KO) displayed a diet-dependent metabolic dysregulation. When fed with normal chow, KO mice show similar body weight, food intake, and energy expenditure as control WT mice. However, KO mice are resistant to high-fat diet (HFD)- induced obesity even though they consume slightly more food. Energy expenditure and the temporal pattern of food intake was altered in the KO mice fed with HFD when compared to control. These findings revealed the pivotal role of Nr1d1 and Nr1d2 of the POMC neurons in regulating the eating behavior and energy expenditure.
W. Zhou: None. T. Yang: None. X. Li: None. Z. Sun: None.
American Diabetes Association (1-19-PDF-012 to W.Z.)