Asprosin: A Novel Adipokine in metabolic syndrome

Hypertension is a leading risk factor for cardiovascular disease and is strongly associated with metabolic syndrome (MS), particularly obesity, through complex and multifactorial mechanisms. Asprosin, a recently discovered adipokine, has been positively correlated with several metabolic conditions, including obesity, type 2 diabetes, polycystic ovary syndrome (PCOS), fatty liver disease, and cardiovascular diseases such as coronary artery disease and hypertension. Asprosin's two well-characterized metabolic roles include promoting hepatic gluconeogenesis and stimulating appetite by activating AgRP+ neurons in the hypothalamus. Additionally, we recently identified a third function of asprosin, Asprosin signaling in the Purkinje neuron of the cerebellum modulates thirst. We have identified Ptprd (Protein Tyrosine Phosphatase type delta) as the neural receptor that asprosin engages for appetite and thirst stimulation. We have developed asprosin and Ptprd targeting therapeutics for treatment of metabolic syndrome. Anti-asprosin monoclonal antibodies and Ptprd-ligand binding domain correct hyperglycemia and hyperphagia in mice models of metabolic syndrome. We have now found that asprosin neutralization with anti-asprosin monoclonal antibodies and small molecule antagonist of Ptprd also treat murine hypertension. Targeting asprosin offers a promising "one remedy for three maladies" therapeutic approach for MS, addressing obesity, type 2 diabetes, and hypertension. COCVD COBRE Pilot grant (P30 GM127211) and DRC Extended Pilot and Feasibility Award, University of Kentucky. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.