Heparin Increases Food Intake through AgRP Neurons

Publication date: 5 September 2017
Source:Cell Reports, Volume 20, Issue 10
Author(s): Canjun Zhu, Pingwen Xu, Yanlin He, Yexian Yuan, Tao Wang, Xingcai Cai, Lulu Yu, Liusong Yang, Junguo Wu, Lina Wang, Xiaotong Zhu, Songbo Wang, Ping Gao, Qianyun Xi, Yongliang Zhang, Yong Xu, Qingyan Jiang, Gang Shu
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.

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Teaser

Zhu et al. demonstrate that 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 is identified as a potential drug target for food intake regulation and body weight control.


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