Contribution of RAS, ROS and COX-1-derived prostanoids to the contractile profile of perivascular adipose tissue in cafeteria diet-induced obesity

Aims: Obesity can lead to the loss of the anticontractile properties of perivascular adipose tissue (PVAT). Given that cafeteria (CAF) diet reflects the variety of highly calorie and easily accessible foods in Western societies, contributing to obesity and metabolic disorders, we sought to investigate the impact of CAF diet on PVAT vasoactive profile and the involvement of renin-angiotensin system, oxidative stress, and cyclooxygenase pathway.

Main methods: Male Balb/c mice received standard or CAF diet for 4 weeks. Oral glucose tolerance and Insulin sensitivity tests were performed, and fasting serum glucose, Cholesterol and triglyceride parameters were determined. Vascular reactivity, fluorescence and immunofluorescence analyzes were carried out in intact thoracic aorta in the presence or absence of PVAT.

Key findings: CAF diet was effective in inducing obesity and metabolic disorders, as demonstrated by increased body weight gain and adiposity index, hyperlipidemia, hyperglycemia, glucose intolerance and Insulin insensitivity. Importantly, CAF diet led to a significant decrease in aortic contractility which was restored in the presence of PVAT, exhibiting therefore a contractile profile. The contractile effect of PVAT was associated with the activation of AT₁ receptor, Reactive Oxygen Species, cyclooxygenase-1, thromboxane A₂ and prostaglandin E₂ receptors.

Significance: These findings suggest that the contractile profile of PVAT involving the renin-angiotensin system activation, Reactive Oxygen Species and cyclooxygenase-1 metabolites may be a protective compensatory adaptive response during early stage of CAF diet-induced obesity as an attempt to restore the impaired vascular contraction observed in the absence of PVAT, contributing to the maintenance of vascular tone.