Dataset Information

Asprosin, a Fasting-Induced Glucogenic Protein Hormone.

ABSTRACT: Hepatic glucose release into the circulation is vital for brain function and survival during periods of fasting and is modulated by an array of hormones that precisely regulate plasma glucose levels. We have identified a fasting-induced protein hormone that modulates hepatic glucose release. It is the C-terminal cleavage product of profibrillin, and we name it Asprosin. Asprosin is secreted by white adipose, circulates at nanomolar levels, and is recruited to the liver, where it activates the G protein-cAMP-PKA pathway, resulting in rapid glucose release into the circulation. Humans and mice with insulin resistance show pathologically elevated plasma asprosin, and its loss of function via immunologic or genetic means has a profound glucose- and insulin-lowering effect secondary to reduced hepatic glucose release. Asprosin represents a glucogenic protein hormone, and therapeutically targeting it may be beneficial in type II diabetes and metabolic syndrome.

SUBMITTER: Romere C

PROVIDER: S-EPMC4852710 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Asprosin, a Fasting-Induced Glucogenic Protein Hormone.

Romere Chase C Duerrschmid Clemens C Bournat Juan J Constable Petra P Jain Mahim M Xia Fan F Saha Pradip K PK Del Solar Maria M Zhu Bokai B York Brian B Sarkar Poonam P Rendon David A DA Gaber M Waleed MW LeMaire Scott A SA Coselli Joseph S JS Milewicz Dianna M DM Sutton V Reid VR Butte Nancy F NF Moore David D DD Chopra Atul R AR

Cell 20160414 3

Hepatic glucose release into the circulation is vital for brain function and survival during periods of fasting and is modulated by an array of hormones that precisely regulate plasma glucose levels. We have identified a fasting-induced protein hormone that modulates hepatic glucose release. It is the C-terminal cleavage product of profibrillin, and we name it Asprosin. Asprosin is secreted by white adipose, circulates at nanomolar levels, and is recruited to the liver, where it activates the G ...[more]

PMID: 27087445

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Project description:BackgroundThe genetic background of Growth Hormone (GH) secretion is not well understood. Mutations giving rise to a stop codon have a high likelihood of affecting protein function.ObjectivesTo analyze likely functional stop codon mutations that are associated with fasting plasma concentration of Growth Hormone.MethodsWe analyzed stop codon mutations in 5451 individuals in the Malmö Diet and Cancer study by genotyping the Illumina Exome Chip. To enrich for stop codon mutations with likely functional effects on protein function, we focused on those disrupting >80% of the predicted amino acid sequence, which were carried by ≥ 10 individuals. Such mutations were related to GH concentration, measured with a high sensitivity assay (hs-GH) and, if nominally significant, to GH related phenotypes, using linear regression analysis.ResultsTwo stop codon mutations were associated with the fasting concentration of hs-GH. rs121909305 (NP_005370.1:p.R93*) [Minor Allele Frequency (MAF) = 0.8%] in the Myosin 1A gene (MYO1A) was associated with a 0.36 (95%CI, 0.04 to 0.54; p=0.02) increment of the standardized value of the natural logarithm of hs-GH per 1 minor allele and rs35699176 (NP_067040.1:p.Q100*) in the Zink Finger protein 77 gene (ZNF77) (MAF = 4.8%) was associated with a 0.12 (95%CI, 0.02 to 0.22; p = 0.02) increase of hs-GH. The mutated high hs-GH associated allele of MYO1A was related to lower BMI (β-coefficient, -0.22; p = 0.05), waist (β-coefficient, -0.22; p = 0.04), body fat percentage (β-coefficient, -0.23; p = 0.03) and with higher HDL (β-coefficient, 0.23; p = 0.04). The ZNF77 stop codon was associated with height (β-coefficient, 0.11; p = 0.02) but not with cardiometabolic risk factors.ConclusionWe here suggest that a stop codon of MYO1A, disrupting 91% of the predicted amino acid sequence, is associated with higher hs-GH and GH-related traits suggesting that MYO1A is involved in GH metabolism and possibly body fat distribution. However, our results are preliminary and need replication in independent populations.

Dataset Information

Asprosin, a Fasting-Induced Glucogenic Protein Hormone.

Publications

Asprosin, a Fasting-Induced Glucogenic Protein Hormone.

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