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Nat Med. 2017 Dec;23(12):1444-1453. doi: 10.1038/nm.4432. Epub 2017 Nov 6.

Asprosin is a centrally acting orexigenic hormone.

Author information

1
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA.
2
USDA-ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
3
Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, Maryland, USA.
4
National Institute on Drug Abuse (NIDA), National Institutes of Health, Baltimore, Maryland, USA.
5
Kennedy Krieger Institute, Baltimore, Maryland, USA.
6
Center for Precision Health, School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, Texas, USA.
7
Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA.
8
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.

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 cAMP-dependent 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.

PMID:
29106398
PMCID:
PMC5720914
DOI:
10.1038/nm.4432
[Indexed for MEDLINE]
Free PMC Article

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