Sulfhydration of perilipin 1 is involved in the inhibitory effects of cystathionine gamma lyase/hydrogen sulfide on adipocyte lipolysis.

Hydrogen sulfide (H₂S) is a novel adipokine mediating glucose uptake, lipid storage and mobilization, thus contributing to the genesis of obesity and associated diseases. Our previous work demonstrated that H₂S inhibited isoproterenol-stimulated lipolysis by reducing the phosphorylation of perilipin 1 (plin-1), a lipid-droplet protein blocking lipase access. How H₂S modulates plin-1 phosphorylation is still unclear. Our present study found that an H₂S donor slightly increased adipose tissue weight and reduced lipolysis in mice; by contrast, deleting the key H₂S generation enzyme cystathionine gamma lyase (CSE) in adipocytes lowered adipose accumulation and enhanced lipolysis. Intriguingly, an H₂S donor induced sulfhydration of plin-1 but not hormone-sensitive lipase, and CSE deletion abolished the post-translational modification of plin-1. During isoproterenol-stimulated lipolysis, plin-1 sulfhydration was associated with reduced phosphorylation, and removing sulfhydration by dithiothreitol recovered the phosphorylation. Finally, plin-1 knockout abolished the effect of H₂S on lipolysis, which indicates that plin-1 sulfhydration is a major direct target of H₂S in lipolysis. We have identified a new post-translation modification, sulfhydration (direct action by H₂S) of plin-1, causing reduced phosphorylation then decreased lipolysis. This finding also highlights a novel molecular regulatory mechanism of lipolysis.

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