Thermoneutral-housed rats demonstrate impaired perivascular adipose tissue and vascular crosstalk.

Abstract

Objective: Vascular pathology, characterized by impaired vasoreactivity and mitochondrial respiration, differs between the sexes. Housing rats under thermoneutral (TN) conditions causes vascular dysfunction and perturbed metabolism. We hypothesized that thoracic perivascular adipose tissue (tPVAT), a vasoregulatory adipose depot known to have a brown adipose tissue (BAT) phenotype, remodels to a mainly white adipose (WAT) phenotype in rats housed at TN, driving diminished vasoreactivity in a sex-dependent manner.

Methods: Male and female Wistar rats were housed at either room temperature (RT) or TN. We measured changes in tPVAT morphology, vasoreactivity in vessels with intact tPVAT or transferred to tPVAT of the oppositely-housed animal, vessel stiffness, vessel mitochondrial respiration and cellular signaling.

Results: Remodeling of tPVAT was observed in rats housed at TN; animals in this environment showed tPVAT whitening and displayed diminished aortae vasodilation (P < 0.05), different between the sexes. Juxtaposing tPVAT from RT rats onto aortae from TN rats in females corrected vasodilation (P < 0.05); this did not occur in males. In aortae of all animals housed at TN, mitochondrial respiration was significantly diminished in lipid substrate experiments (P < 0.05), and there was significantly less expression of phosphorylated endothelial nitric oxide synthase (peNOS) (P < 0.001).

Conclusions: These data are consistent with TN-induced remodeling of tPVAT, notably associated with sex-specific blunting of vasoreactivity, diminished mitochondrial respiration, and altered cellular signaling.