Sex Specific Effects of Obesity on Perivascular Adipose Tissue and Aortic Reactivity

Abstract

Obesity is a societally prevalent disorder that affects men and women indiscriminately. Nationally, it has become a healthcare concern that impacts the wellness of 40% of US adults as per the US CDC. One disparaging issue implicated with the emerging obesity epidemic is damage to the cardiovascular system, and its differential effects on men and women. While cellular pathways primary to vascular tissue itself certainly play a role in obesity related vascular dysfunction; the condition of fat tissue surrounding vessels may also be implicated. A sex equipoised study of perivascular adipose tissue (PVAT) could potentially shed light onto the varying rates of cardiovascular health decline in men and women associated with obesity.17‐week‐old male and female, lean and obese Zucker rats (n=5 for all groups LZR/OZR) were used in this study. 2mm sections of thoracic aorta were dissected from the LZRs and OZRs. Aortic segments were mounted on a pin myograph system (DMT‐620m, AD Instruments) containing warm aerated physiological saline solution. PVAT conditioned media (PVATcm, 200mg/ml) was prepared using PVAT dissected from male and female LZR and OZR thoracic aortas. Vessels were pre‐constricted with phenylephrine (10−6M) and exposed to intensifying doses of methacholine (10−9M to 10−4M) resulting in a dose‐dependent curve used to assess baseline endothelial‐dependent relaxation (EDR). These methods were repeated and new measures were recorded after a 30min incubation with PVATcm that was native to the aortic segment. Subsequently, phenylephrine (10−9−4M) and sodium nitroprusside (SNP;10−9−4M) were used to assess endothelial‐independent relaxation and to measure total constriction. All data were analyzed via STATVIEW, using a one‐way ANOVA with significance p≤ 0.05.Male and female LZR had similar native aortic (without PVATcm) EDR (83% ± 1.5 vs. 90% ± 1.4 respectively). Incubating the LZR male and female aorta with their respective LZR PVATcm showed minor improvement in EDR (87% ± 1.6 and 94% ± 2.0). Male and female OZR native aortic EDR (64% ± 2.0 vs. 81% ± 1.7) was significantly lower compared to the male and female LZR native aorta. Incubating the female OZR aorta with their PVATcm did not significantly affect EDR (85% ± 4.4). In contrast, the male OZR aorta incubated with their PVATcm significantly reduced EDR (58% ± 2.1).These data indicate that the vasculature of obese animals is inherently damaged vs. lean animals. They also suggest that lean PVAT tissue may be advantageous to vascular health in both sexes. They further indicate that PVAT in obese males is involved in cardiovascular dysfunction, but PVAT in obese female animals elicit a response opposite of this. This suggests there may be biochemical factors present in the PVAT of obese females protecting them from cardiovascular dysfunction. The male/female dichotomy of EDR exemplified in this investigation requires further study to determine cellular pathways that may contribute to this protective mechanism.Support or Funding InformationWVINBRE: NIH Grant P20GM103434 WVCTSI : NIGM Grant 5U54GM104942‐03This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.