Aerobic Exercise Attenuates Obesity-Associated Vascular Dysfunction via Restoration of Perivascular Adipose Tissue Homeostasis in Mice.

Abstract

Purpose: Perivascular adipose tissue (PVAT) dysfunction contributes to vascular impairment in obesity, primarily through altered lipid accumulation, inflammatory cytokine imbalance, and disrupted endothelial signaling. This study aimed to investigate whether aerobic exercise can ameliorate PVAT-induced vascular dysfunction in mice with obesity induced by a high-fat diet.

Methods: Male C57BL/6J mice were fed either a chow or a high-fat diet for 12 weeks, followed by 8 weeks of aerobic treadmill training or sedentary control. Body weight, PVAT morphology, and levels of inflammatory cytokines (tumor necrosis factor alpha, interleukin 1β, monocyte chemoattractant protein 1, and intercellular adhesion molecule 1), adipokines (leptin and adiponectin), and phosphorylation of endothelial signaling proteins (Akt, AMP-activated protein kinase [AMPK], and endothelial nitric oxide synthase [eNOS]) were evaluated in the thoracic aorta and PVAT. Endothelium-dependent relaxation (EDR) was assessed using acetylcholine-induced vasodilation in aortic rings with or without PVAT.

Results: High-fat diet-induced obesity led to increased adipocyte size in PVAT, while it also impaired vascular relaxation, elevated levels of proinflammatory cytokines, and reduced phosphorylation of Akt, AMPK, and eNOS in both PVAT and the aorta. Aerobic exercise training significantly reduced PVAT adipocyte size, restored EDR, suppressed inflammatory cytokine levels, increased adiponectin expression, and promoted phosphorylation of vascular signaling molecules in both PVAT and the aorta.

Conclusion: Aerobic exercise training restores PVAT homeostasis and endothelial function in obese mice by modulating inflammation, adipokines, and vascular signaling. These findings suggest aerobic exercise as a nonpharmacological approach to improve vascular function in obesity by targeting PVAT dysfunction.