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Title: Asprosin, a fasting-induced glucogenic protein hormone

Author
item ROMERE, CHASE - Baylor College Of Medicine
item DUERRSCHMID, CLEMENS - Baylor College Of Medicine
item BOURNAT, JUAN - Baylor College Of Medicine
item CONSTABLE, PETRA - Baylor College Of Medicine
item JAIN, MAHIM - Baylor College Of Medicine
item XIA, FAN - Baylor College Of Medicine
item SAHA, PRADIP - Baylor College Of Medicine
item DEL SOLAR, MARIA - The Icahn School Of Medicine At Mount Sinai
item ZHU, BOKAI - Baylor College Of Medicine
item YORK, BRIAN - Baylor College Of Medicine
item SARKAR, POONAM - Children'S Nutrition Research Center (CNRC)
item RENDON, DAVID - Children'S Nutrition Research Center (CNRC)
item GABER, M - Children'S Nutrition Research Center (CNRC)
item LEMAIRE, SCOTT - Baylor College Of Medicine
item COSELLI, JOSEPH - Baylor College Of Medicine
item MILEWICZ, DIANNA - University Of Texas Medical Branch
item SUTTON, V - Baylor College Of Medicine
item BUTTE, NANCY - Children'S Nutrition Research Center (CNRC)
item MOORE, DAVID - Baylor College Of Medicine
item CHOPRA, ATUL - Baylor College Of Medicine

Submitted to: Cell
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/23/2016
Publication Date: 4/14/2016
Citation: Romere, C., Duerrschmid, C., Bournat, J., Constable, P., Jain, M., Xia, F., Saha, P.K., Del Solar, M., Zhu, B., York, B., Sarkar, P., Rendon, D.A., Gaber, M.W., Lemaire, S.A., Coselli, J.S., Milewicz, D.M., Sutton, V.R., Butte, N.F., Moore, D.D., Chopra, A.R. 2016. Asprosin, a fasting-induced glucogenic protein hormone. Cell. 165:566-579.

Interpretive Summary: Investigators at Baylor College of Medicine discovered a new hormone, named Asprosin, that is critical for the regulation of circulating levels of glucose. Asprosin is secreted by fat tissue and acts on the liver where it stimulates the release of glucose into the blood. In the future, altering the levels of Asprosin by pharmaceutical means may benefit individuals with diabetes and the metabolic syndrome.

Technical Abstract: Hepatic glucose release into the circulation is vital for brain function and survival during periods of fasting and is modulated by an array of hormones that precisely regulate plasma glucose levels. We have identified a fasting-induced protein hormone that modulates hepatic glucose release. It is the C-terminal cleavage product of profibrillin, and we name it Asprosin. Asprosin is secreted by white adipose, circulates at nanomolar levels, and is recruited to the liver, where it activates the G protein-cAMP-PKA pathway, resulting in rapid glucose release into the circulation. Humans and mice with insulin resistance show pathologically elevated plasma asprosin, and its loss of function via immunologic or genetic means has a profound glucose- and insulin-lowering effect secondary to reduced hepatic glucose release. Asprosin represents a glucogenic protein hormone, and therapeutically targeting it may be beneficial in type II diabetes and metabolic syndrome.