Effects of High-Fat and High-Fat/High-Sucrose Diet-Induced Obesity on PVAT Modulation of Vascular Function in Male and Female Mice

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.

The Role of Obesity-Induced Perivascular Adipose Tissue (PVAT) Dysfunction in Vascular Homeostasis

“…The authors concluded that the potential mechanisms underlying these effects may be related to the different adipocyte species that comprise tPVAT and aPVAT [131]. Victorio et al reported that the effect of HF and HS diets on PVAT differs depending on sex [132]. The anti-contractile effect of PVAT was measured by comparing the phenylephrine-induced contraction in mesenteric arteries after 3 and 5 months of HF or HF+HS diet among male and female mice.…”

Perivascular Adipose Tissue Compensation for Endothelial Dysfunction in the Superior Mesenteric Artery of Female SHRSP.Z-<i>Lepr</i>^<i>fa</i>/IzmDmcr Rats

“…In contrast to our study, a beneficial PVAT function (anticontractile activity) was shown to be retained in the aortas of male Dahl salt-sensitive rats that were fed a high-fat diet for 24 weeks (from 3 weeks), but not in females [26]. Similarly to the study into Dahl salt-sensitive rats, the anti-contractile PVAT function was found to be impaired for 3-5 months in the superior mesenteric arteries of female C57Bl/6 mice, following administration of a highfat or high-fat plus high-sucrose diet from 2 months of age, but was preserved in males [40]. However, sex-related differences have often been either unreported or not considered during experimental design in preclinical research, so we cautiously interpret our results as evidence that PVAT function varies by sex.…”

“…PVAT has been found to have no effect on endothelium-dependent methacholine-induced relaxation in the aortas of obese female Zucker rats [23], although it has been shown to impair relaxation in males [24]. Through the administration of a high-fat diet, PVAT anti-contractile effects have been shown to be impaired in the superior mesenteric arteries of female C57Bl6 mice [25], and in the aortas of female Dahl salt-sensitive rats [26], but not in the arteries of corresponding males. In contrast, PVAT-assisted stress relaxations in the aortas of Dahl salt-sensitive rats did not differ between sexes [27].…”

Insights by which TUDCA is a potential therapy against adiposity

“…The obesity has also been demonstrated to alter the perivascular adipose tissue (PVAT) ( 58 , 59 ). PVAT presents morphological characteristics that vary according to the vascular bed, resembling WAT in mesenteric arteries and abdominal aorta or BAT/beige in thoracic aorta ( 60 – 62 ).…”