Obesity-related hypertension: the contribution of PPAR gamma acetylation and asprosin

This research aims to clarify the mechanisms by which obesity promotes arterial stiffness and elevated blood pressure, with a focus on perivascular adipose tissue (PVAT) and the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ), both of which normally exert protective effects on vascular function. Preliminary findings show that mice fed a Western diet develop obesity, increased aortic stiffness, and hypertension, accompanied by hyperacetylation of PPARγ in PVAT. These changes are also associated with elevated levels of asprosin, a recently identified adipokine, in serum, aortic tissue, and mesenteric PVAT. Functional studies further demonstrate that asprosin directly impairs vascular function by enhancing vasoconstriction and reducing vasodilation.

Importantly, mice genetically engineered to mimic PPARγ deacetylation (2KR mice) exhibited reduced aortic stiffness despite consuming a Western diet, suggesting a protective role for PPARγ deacetylation. The central hypothesis of this project is that a PPARγ hyperacetylation–asprosin signaling pathway in adipose tissue contributes to obesity-related arterial stiffness and hypertension. Two specific aims will test this hypothesis by examining vascular outcomes in 2KR mice and determining whether asprosin acts downstream of PPARγ hyperacetylation.

Overall, this work seeks to identify PPARγ deacetylation as a novel therapeutic target for treating hypertension in obese patients, while advancing understanding of obesity-driven vascular disease and fostering clinically relevant research opportunities.