TAp63 contributes to sexual dimorphism in POMC neuron functions and energy homeostasis

• DOI: 10.1038/s41467-018-03796-7
• Publication Date: 2018-04-12T14:42:15Z
• Authors: Chunmei Wang; Yanlin He; Pingwen Xu; Yongjie Yang; Kenji Saito; Yan Xia; Xiaofeng Yan; Antentor Hinton Jr; Chunling Yan; Hongfang Ding; Likai Yu; Gang Shu; Rajat Gupta; Qi Wu; Qingchun Tong; William R. Lagor; Elsa R. Flores; Yong Xu
• Keywords: Male; Neurons; 0301 basic medicine; 2. Zero hunger; Sex Characteristics; Pro-Opiomelanocortin; Science; Q; Body Weight; Arcuate Nucleus of Hypothalamus; Hypothalamus; Estrogens; Phosphoproteins; Article; Mice; 03 medical and health sciences; Sex Factors; Trans-Activators; Animals; Homeostasis; Receptors, Leptin; Female; Obesity; Energy Metabolism

AbstractSexual dimorphism exists in energy balance, but the underlying mechanisms remain unclear. Here we show that the female mice have more pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of hypothalamus than males, and female POMC neurons display higher neural activities, compared to male counterparts. Strikingly, deletion of the transcription factor, TAp63, in POMC neurons confers “male-like” diet-induced obesity (DIO) in female mice associated with decreased POMC neural activities; but the same deletion does not affect male mice. Our results indicate that TAp63 in female POMC neurons contributes to the enhanced POMC neuron functions and resistance to obesity in females. Thus, TAp63 in POMC neurons is one key molecular driver for the sexual dimorphism in energy homeostasis.