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
Date Published2017 Dec
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

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.

Alternate JournalNat. Med.
PubMed ID29106398
PubMed Central IDPMC5720914
Grant ListK08 DK102529 / DK / NIDDK NIH HHS / United States
P30 CA016086 / CA / NCI NIH HHS / United States
R01 DK093587 / DK / NIDDK NIH HHS / United States
R01 DK101379 / DK / NIDDK NIH HHS / United States