Reduced adipose tissue H2S in obesity

Abstract

Hydrogen sulfide (H₂S) is an endogenously produced signaling molecule synthesized by cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST). Given that H₂S exerts significant effects on bioenergetics and metabolism, the goal of the current study was to determine the expression of H₂S-producing enzymes in adipose tissues in models of obesity and metabolic disruption. Mice fed a western diet expressed lower mRNA levels of all three enzymes in epididymal fat (EWAT), while only CSE and 3-MST were reduced in brown adipose tissue (BAT). At the protein level 3-MST was reduced in all fat depots studied. Using db/db mice, a genetic model of obesity, we found that CSE, CBS and 3-MST mRNA were reduced in white fat, while only CSE was reduced in BAT. CBS and CSE protein levels were suppressed in all three fat depots. In a model of age-related weight gain, no reduction in the mRNA of any of the enzymes was noted. Smaller amounts of 3-MST protein were found in EWAT, while both CSE and 3-MST were reduced in BAT. Tissue levels of H₂S were lower in WAT in HFD mice; both WAT and BAT contained lower H₂S amounts in db/db animals. Taken together, our data suggest that obesity is associated with a decreased expression of H₂S-synthesizing enzymes and reduced H₂S levels in adipose tissues of mice. We propose that the reduction in H₂S may contribute to the metabolic response associated with obesity. Further work is needed to determine whether restoring H₂S levels may have a beneficial effect on obesity-associated metabolic alterations.

Keywords: 3-Mercaptopyruvate sulfurtransferase; Cystathionine β-synthase; Cystathionine γ-lyase; Hydrogen sulfide; Obesity.