Asprosin is a centrally acting orexigenic hormone

Authors: DUERRSCHMID, CLEMENS - Baylor College Of Medicine; HE, YANLIN - Children'S Nutrition Research Center (CNRC); WANG, CHUNMEI - Children'S Nutrition Research Center (CNRC); LI, CHIA - National Institutes Of Health (NIH); BOURNAT, JUAN - Baylor College Of Medicine; ROMERE, CHASE - Baylor College Of Medicine; SAHA, PRADIP - Baylor College Of Medicine; LEE, MARK - Baylor College Of Medicine; PHILLIPS, KEVIN - Baylor College Of Medicine; JIA, PEILIN - University Of Texas Health Science Center; ZHAO, ZHONGMING - University Of Texas Health Science Center; FARIAS, MONICA - Children'S Nutrition Research Center (CNRC); WU, QI - Children'S Nutrition Research Center (CNRC); MILEWICZ, DIANNA - University Of Texas Health Science Center; SUTTON, REID - Baylor College Of Medicine; MOORE, DAVID - Baylor College Of Medicine; BUTTE, NANCY - Children'S Nutrition Research Center (CNRC); KRASHES, MICHAEL - National Institutes Of Health (NIH); XU, YONG - Children'S Nutrition Research Center (CNRC); CHOPRA, ATUL - Baylor College Of Medicine

Submitted to: Nature Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/3/2017
Publication Date: 11/6/2017
Citation: Duerrschmid, C., He, Y., Wang, C., Li, C., Bournat, J., Romere, C., Saha, P., Lee, M., Phillips, K., Jia, P., Zhao, Z., Farias, M., Wu, Q., Milewicz, D., Sutton, R., Moore, D., Butte, N., Krashes, M., Xu, Y., Chopra, A. 2017. Asprosin is a centrally acting orexigenic hormone. Nature Medicine. https://doi.org/10.1038/nm.4432.

Interpretive Summary: Obesity is a serious global health problem. Here we showed that asprosin, a newly discovered hormone, can increase food intake and body weight via its actions in the brain. These findings suggest that asprosin could be a potential target for treatment of obesity.

Technical Abstract: Asprosin is a recently discovered fasting-induced hormone that promotes hepatic glucose production. Here we demonstrate that asprosin in the circulation crosses the blood–brain barrier and directly activates orexigenic AgRP+ neurons via a cAMPdependent pathway. This signaling results in inhibition of downstream anorexigenic proopiomelanocortin (POMC)-positive neurons in a GABA-dependent manner, which then leads to appetite stimulation and a drive to accumulate adiposity and body weight. In humans, a genetic deficiency in asprosin causes a syndrome characterized by low appetite and extreme leanness; this is phenocopied by mice carrying similar mutations and can be fully rescued by asprosin. Furthermore, we found that obese humans and mice had pathologically elevated concentrations of circulating asprosin, and neutralization of asprosin in the blood with a monoclonal antibody reduced appetite and body weight in obese mice, in addition to improving their glycemic profile. Thus, in addition to performing a glucogenic function, asprosin is a centrally acting orexigenic hormone that is a potential therapeutic target in the treatment of both obesity and diabetes.