Dietary methionine depletion and hydrogen sulfide-producing genes in perivascular adipose tissue of male Wistar rats.

Perivascular adipose tissue (PVAT) regulates vascular tone, and high-fat diets reportedly lead to the loss of its anti-contractile properties. Methionine restriction recapitulates many caloric restriction metabolic effects and increases liver expression of activating transcription factor 4 (ATF4) and downstream targets with anti-contractile properties such as cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE). We hypothesized that dietary methionine restriction would prevent high-fat diet-induced PVAT dysfunction by increasing ATF4 expression. Male Wistar rats were fed control (C, 10% calories from fat) or high-fat diets (H, 60% calories from fat) (HFD) that were methionine replete (R, 0.86% methionine) or deplete (D, 0.12% methionine) for 12 weeks. Methionine restriction prevented body mass increases, independent of fat content, and had no effect on blood pressure or arterial contraction to norepinephrine (10 μM) or relaxation to acetylcholine (10 μM). In this feeding paradigm, HFD did not induce PVAT dysfunction. CR diet increased ATF4 transcript levels in multiple PVAT depots but did not consistently affect expression of downstream targets. Protein expression of ATF4 and its targets varied largely for all groups. In conclusion, 12 week methionine restriction profoundly affected body mass but not blood pressure or arterial reactivity in the presence or absence of PVAT.