Hydrogen sulfide impacts on inflammation-induced adipocyte dysfunction

Abstract

A dual role of hydrogen sulfide (H₂S) in inflammation is well-reported and recent studies demonstrated adipogenic effects of H₂S in 3T3-L1 cells. Here, we aimed to investigate the effects of H₂S on adipocyte differentiation and inflammation. H₂S concentration in 3T3-L1 culture media was increased during adipocyte differentiation in parallel to adipogenic and Cth gene expression, and its inhibition using DL-Propargyl Glycine (PPG) impaired 3T3-L1 differentiation. GYY4137 and Na₂S administration only in the first or in the last stage of adipocyte differentiation resulted in a significant increased expression of adipogenic genes. However, when GYY4137 or Na₂S were administrated during all process no significant effects on adipogenic gene expression were found, suggesting that excessive H₂S administration might exert negative effects on adipogenesis. In fact, continuous addition of Na₂S, which resulted in Na₂S excess, inhibited adipogenesis, whereas time-expired Na₂S had no effect. In inflammatory conditions, GYY4137, but not Na₂S, administration attenuated the negative effects of inflammation on adipogenesis and insulin signaling-related gene expression during adipocyte differentiation. In inflamed adipocytes, Na₂S administration enhanced the negative effects of inflammatory process. Altogether these data showed that slow-releasing H₂S improved adipocyte differentiation in inflammatory conditions, and that H₂S proadipogenic effects depend on dose, donor and exposure time.

Keywords: 3T3-L1; 3T3-L1 cell differentiation; Adipocyte; GYY4137; Hydrogen sulfide; Inflammation; Na(2)S.