Asprosin — New Hormone Involved in Hepatic Glucose Release

RESEARCH HIGHLIGHTS

Nature Reviews Endocrinology | Published online 29 Apr 2016; doi:10.1038/nrendo.2016.66

LIVER Asprosin — new hormone involved in hepatic glucose release

A new hormone, named asprosin, Furthermore, Chopra and colleagues The research team also measured has been identified by a team of found that mice with a genetic plasma levels of asprosin in eight men …a single researchers in the USA. Asprosin is ablation of adipose tissue (Bscl2–/– who had insulin resistance and eight secreted by white adipose tissue and mice) had a twofold reduction in healthy control individuals, which injection induces hepatic glucose release, mak- plasma levels of asprosin compared revealed that asprosin levels were of asprosin ing this protein a potential target for with wild-type mice. In addition, increased in men with insulin resist- resulted in an new therapeutics for type 2 diabetes mature adipocytes in culture were ance. These findings were confirmed immediate mellitus and obesity. able to generate and secrete asprosin, in two mouse models of insulin Several years ago, Atul Chopra whereas preadipocytes were not. resistance. An asprosin-specific increase in (corresponding author on the new These findings confirmed adipose monoclonal antibody reduced plasma blood glucose article) identified two patients with tissue as a source of asprosin. levels of asprosin in these mice, and levels… neonatal progeroid syndrome who In mice, a single injection of improved insulin sensitivity. were insulin sensitive despite having asprosin resulted in an immediate Chopra highlights that this paper lipodystrophy. In the current paper, increase in blood glucose levels, raises many new questions. For the research team set out to explain leading to hyperinsulinaemia and instance, the receptor for asprosin this anomaly. Whole exome and normalization of blood glucose lev- is yet to be identified and the fac- Sanger sequencing revealed that both els within 60 mins of the injection. tors that regulate its secretion are patients had a truncating mutation in As the liver is the main site for glu- unknown. Chopra and his colleagues FBN1 (which encodes profibrillin). cose storage, this finding suggests are working to answer these questions This mutation resulted in the loss of that the liver is a target organ for and also hope to determine whether the C-terminal cleavage product asprosin. The investigators were the anti-asprosin antibodies could be of profibrillin, which the research- also able to show that asprosin effective treatments for type 2 diabe- ers named asprosin, a previously induces hepatic glucose production tes mellitus and obesity. “These are unknown hormone. by using cAMP as a second mes- early but exciting days in the field of Using the Genotype-Tissue senger. “This is a critical function asprosin biology,” concludes Chopra. Expression Project RNA-Seq data of the liver during fasting, and is Claire Greenhill set, the researchers were able to necessary for normal brain function

determine that adipose tissue has between meals,” explains Chopra. ORIGINAL ARTICLE Romere, C. et al. Asprosin, the highest FBN1 mRNA expression “Indeed, fasting increases asprosin a fasting-induced gluconeogenic protein level, which suggests that adipose levels in the blood while feeding hormone. Cell http://dx.doi.org/10.1016/ j.cell.2016.02.063 (2016) Jennie Vallis/NPG tissue is the source of asprosin. turns off its production.”