Abstract
Increased adiposity in perivascular adipose tissue (PVAT) has been related to vascular dysfunction. High-fat (HF) diet-induced obesity models are often used to analyze the translational impact of obesity, but differences in sex and Western diet type complicate comparisons between studies. The role of PVAT was investigated in small mesenteric arteries (SMAs) of male and female mice fed a HF or a HF plus high-sucrose (HF + HS) diet for 3 or 5 months and compared them to age/sex-matched mice fed a chow diet. Vascular responses of SMAs without (PVAT-) or with PVAT (PVAT+) were evaluated. HF and HF + HS diets increased body weight, adiposity, and fasting glucose and insulin levels without affecting blood pressure and circulating adiponectin levels in both sexes. HF or HF + HS diet impaired PVAT anticontractile effects in SMAs from females but not males. PVAT-mediated endothelial dysfunction in SMAs from female mice after 3 months of a HF + HS diet, whereas in males, this effect was observed only after 5 months of HF + HS diet. However, PVAT did not impact acetylcholine-induced relaxation in SMAs from both sexes fed HF diet. The findings suggest that the addition of sucrose to a HF diet accelerates PVAT dysfunction in both sexes. PVAT dysfunction in response to both diets was observed early in females compared to age-matched males suggesting a susceptibility of the female sex to PVAT-mediated vascular complications in the setting of obesity. The data illustrate the importance of the duration and composition of obesogenic diets for investigating sex-specific treatments and pharmacological targets for obesity-induced vascular complications.
Highlights
IntroductionExcessive body fat storage (i.e., increased intake energy with reduced energy expenditure) is a major feature of obesity
Excessive body fat storage is a major feature of obesity
The present study investigated whether two different HF obesogenic diets (60% HF versus 45% HF plus high sucrose) impact Perivascular adipose tissue (PVAT) anticontractile function differentially in males and females over time
Summary
Excessive body fat storage (i.e., increased intake energy with reduced energy expenditure) is a major feature of obesity This condition results in chronic low-grade inflammation presenting a more complex resolution and represents a risk factor for the development and/or worsening of several chronic diseases, including cardiovascular diseases (CVDs) (Caballero et al, 2008; World Health Organization, 2019). Despite the knowledge of sex-specific differences in the development of obesity and CVDs, few studies have covered obesity-related vascular (dys) function in males and females. Sexual dimorphism in PVAT immune cell content in response to a high-fat (HF) diet was recently demonstrated (Kumar et al, 2021), but it is still unclear whether obesogenic diets differentially impact PVAT anticontractile function in males and females over time
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