Asprosin

Medical

Clinical Definition

Asprosin is a 140 amino acid C-terminal cleavage product of profibrillin, encoded by FBN1 exon 65, secreted by white adipose tissue in response to fasting and low insulin. It acts on hepatocytes through the olfactory receptor OLFR734, increasing cyclic AMP and protein kinase A activity and driving hepatic glucose release through glycogenolysis and gluconeogenesis, and it crosses the blood-brain barrier to activate agouti-related peptide neurons and inhibit pro-opiomelanocortin neurons in the arcuate nucleus, so it is orexigenic. Circulating concentrations are elevated in obesity, insulin resistance, type 2 diabetes, non-alcoholic fatty liver disease and polycystic ovary syndrome, correlate with body mass index, fasting glucose and insulin resistance indices, and are associated with increased hepatic glucose output; consistent with this physiology, patients with neonatal progeroid syndrome and FBN1 mutations have extreme leanness and insulin sensitivity. Experimental neutralisation with a monoclonal antibody in mice reduces appetite and improves glucose tolerance, and receptor blockade has similar effects, supporting a causal role in at least some models. Important caveats are that much of the evidence is preclinical, assay methodology varies between studies and absolute concentrations are difficult to compare, correlations in humans are modest and confounded by adiposity and insulin resistance, and no therapy targeting asprosin is licensed. Clinically, asprosin is a useful explanatory hormone rather than a test or a treatment, and it reinforces two practical points: fasting glucose in obesity reflects active hormone signalling rather than only dietary carbohydrate, and appetite in obesity has a measurable endocrine basis.