Aortic stiffness, endothelial dysfunction and diastolic dysfunction (DD) are cardiovascular (CV) abnormalities seen in obesity associated with consumption of high fat/fructose western diet (WD). Moreover, CV dysfunction is increasingly prevalent in obese women. Herein, we examined whether the DPP-4 inhibitor, linagliptin (LINA), improves these outcomes in WD fed female C57BL/6 mice. Four week old mice were fed control diet (CD) or WD with or without LINA for 16 weeks, after which pulse wave velocity (aortic stiffness) (PWV), echocardiography (diastolic function), atomic force microscopy (endothelial stiffness) and wire myography (aortic vascular reactivity) were performed. Compared to CD mice, WD mice exhibited 21% and 353% higher PWV and endothelial stiffness, respectively. WD induced DD, indicated by impaired septal wall motion (<E’/A’ ratio), left atrial filling pressure (>E/Vp ratio), prolonged isovolumic relaxation time (IVRT) and impaired myocardial performance index (>MPI). These vascular and cardiac abnormalities were prevented by LINA. LINA also prevented WD-induced impairments in acetylcholine-, sodium nitroprusside-, and insulin-mediated aortic vascular relaxation. These results show that LINA exerts CV protection in a translational model of obesity.
