Asprosin is a centrally acting orexigenic hormone.

TitleAsprosin is a centrally acting orexigenic hormone.
Publication TypeJournal Article
Year of Publication2017
AuthorsDuerrschmid, C, He, Y, Wang, C, Li, C, Bournat, JC, Romere, C, Saha, PK, Lee, ME, Phillips, KJ, Jain, M, Jia, P, Zhao, Z, Farias, M, Wu, Q, Milewicz, DM, V Sutton, R, Moore, DD, Butte, NF, Krashes, MJ, Xu, Y, Chopra, AR
JournalNat Med
Volume23
Issue12
Pagination1444-1453
Date Published2017 Dec
ISSN1546-170X
KeywordsAdolescent, Adult, Animals, Appetite Depressants, Appetite Regulation, Female, Humans, Hypothalamus, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Microfilament Proteins, Neurons, Peptide Fragments, Peptide Hormones, Rats, Signal Transduction, Young Adult
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 AgRPneurons 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.

DOI10.1038/nm.4432
Alternate JournalNat. Med.
PubMed ID29106398
PubMed Central IDPMC5720914
Grant ListR01 DK101379 / DK / NIDDK NIH HHS / United States
P30 CA016086 / CA / NCI NIH HHS / United States
UM1 HG006542 / HG / NHGRI NIH HHS / United States
K08 DK102529 / DK / NIDDK NIH HHS / United States
R01 DK111631 / DK / NIDDK NIH HHS / United States
P30 CA125123 / CA / NCI NIH HHS / United States
UM1 HG006348 / HG / NHGRI NIH HHS / United States
R01 LM012806 / LM / NLM NIH HHS / United States
P30 DK079638 / DK / NIDDK NIH HHS / United States