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Title: Asprosin is a centrally acting orexigenic hormone

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