Asprosin is a centrally acting orexigenic hormone

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

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.

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Appetite Depressants / metabolism
  • Appetite Regulation / genetics*
  • Female
  • Humans
  • Hypothalamus / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microfilament Proteins / genetics
  • Microfilament Proteins / physiology*
  • Neurons / metabolism
  • Peptide Fragments / genetics
  • Peptide Fragments / physiology*
  • Peptide Hormones / genetics
  • Peptide Hormones / physiology*
  • Rats
  • Signal Transduction
  • Young Adult

Substances

  • Appetite Depressants
  • Microfilament Proteins
  • Peptide Fragments
  • Peptide Hormones
  • asprosin protein, human