Cholinergic modulation of circuits involved in stress-related behaviors

摘要

Although the widely used anticoagulant drug heparin has been shown to have many other biological functions independent from its anticoagulant role, the effects of heparin on energy homeo- stasis is unknown. Here, we demonstrated that heparin level is negatively associated with nutritional states and heparin treatment increases food intake and body weight gain. By using electrophys- iological, pharmacological, molecular biological and chemogenetic approaches, we provided evidence that heparin increases food intake by stimulating AgRP neurons and increasing AgRP release. Our results support a model 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. For the very first time we identified heparin as a potential drug target for food intake regulation and body weight control.