4 years ago

Heparin Increases Food Intake through AgRP Neurons

Heparin Increases Food Intake through AgRP Neurons
Gang Shu, Canjun Zhu, Xingcai Cai, Lulu Yu, Yexian Yuan, Yong Xu, Pingwen Xu, Ping Gao, Yongliang Zhang, Lina Wang, Tao Wang, Yanlin He, Songbo Wang, Xiaotong Zhu, Liusong Yang, Qingyan Jiang, Junguo Wu, Qianyun Xi


Although the widely used anticoagulant drug heparin has been shown to have many other biological functions independent of its anticoagulant role, its effects on energy homeostasis are unknown. Here, we demonstrate that heparin level is negatively associated with nutritional states and that heparin treatment increases food intake and body weight gain. By using electrophysiological, pharmacological, molecular biological, and chemogenetic approaches, we provide evidence that heparin increases food intake by stimulating AgRP neurons and increasing AgRP release. Our results support a model whereby heparin competes with insulin for insulin receptor binding on AgRP neurons, and by doing so it inhibits FoxO1 activity to promote AgRP release and feeding. Heparin may be a potential drug target for food intake regulation and body weight control.

Publisher URL: http://www.cell.com/cell-reports/fulltext/S2211-1247(17)31174-9

DOI: 10.1016/j.celrep.2017.08.049

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