Hypothalamic extended synaptotagmin-3 contributes to the development of dietary obesity and related metabolic disorders
Yi Zhang, Yunliang Guan, Susu Pan, Lihong Yan, Ping Wang, Zhuo Chen, Qing Shen, Faming Zhao, Xin Zhang, Juan Li, Juan Li, Juxue Li, Juxue Li, Dongsheng Cai, Guo Zhang
Abstract
Significance The epidemic of obesity has reached an alarming level worldwide. Understanding the etiology of obesity is important for identifying a new approach of prevention or treatment. Accumulating evidence demonstrates that the central nervous system plays a critical role in animal’s energy homeostasis. Here, we show that extended synaptotagmin (E-Syt3) is expressed in the hypothalamus and contributes to diet-induced obesity development. Whole-body or proopiomelanocortin neuron-specific deletion of E-Syt3 significantly protects mice against DIO and related metabolic disorders. Mechanistically, we show that inhibition of E-Syt3 can lead to increased hypothalamic content of α-melanocyte-stimulating hormone. Thus, our current work suggests that E-Syt3 might be a relevant target for treating obesity.