COBRE Pilot: The Role of Novel Adipokine Asprosin in Cardiovascular Health

Asprosin is a recently discovered metabolic adipokine, found highly associated with obesity and various other metabolic syndrome conditions including hypertension. So far, two spatio- temporally distinct metabolic functions of asprosin have been documented. Asprosin cell- autonomously promotes hepatic gluconeogenesis via the G protein- coupled receptor pathway and promotes feeding behavior via the tyrosine phosphatase receptor pathway of the AgRP (Agouti related peptide) neurons of the hypothalamus. Given the widespread expression of asprosin’s neural receptor, we expect asprosin has additional non-canonical neural functions we have not yet discovered. We have found the blood pressure modulatory function of asprosin, independent of its glucogenic and orexigenic function. Asprosin deficient mice (genetic mice model of Neonatal progeroid syndrome) have hypotension that can be completely rescued with acute ectopic asprosin treatment. Further, our preliminary data indicates the possibility that asprosin’s blood pressure regulatory effects are mediated through the oxytocin neurons of the hypothalamus. Female mice with genetic loss of Ptprd from oxytocin+ neurons show mild hypotension when subjected to tail-cuff Volume Pressure Recording system. Confirmation & validation of our blood pressure assessment using telemetry is imperative to ascertain the role of oxytocin neuron specific asprosin-Ptprd signaling in regulation of blood pressure. Furthermore, we have previously demonstrated that anti-asprosin monoclonal antibodies (mAbs) display a dose- dependent in vivo efficacy at lowering appetite and improving blood glucose. We now report that mAb treatment also significantly lowers the blood pressure in mice. This suggests mAb therapeutic as ‘one remedy for obesity, type II diabetes & hypertension. We seek to test the relationship between asprosin and blood pressure and ask two questions: does asprosin-Ptprd signaling in the oxytocin neurons modulate blood pressure of mice and can neutralization of asprosin be used as a therapeutic for treatment of MS associated hypertension. We will address these two questions in the following 2 studies: (1) Assessment of blood pressure of mice with genetic loss of Ptprd from oxytocin neurons using telemetry. (2) Assessment of the effects of antiasprosin monoclonal antibody treatment on the blood pressure of Db/Db mice.