Hydrogen Sulfide in the Adipose Tissue—Physiology, Pathology and a Target for Pharmacotherapy

Hydrogen sulfide (H(2)S) is synthesized in the adipose tissue mainly by cystathionine γ-lyase (CSE). Several studies have demonstrated that H(2)S is involved in adipogenesis, that is the differentiation of preadipocytes to adipocytes, most likely by inhibiting phosphodiesterases and increasing cyclic AMP concentration. The effect of H(2)S on adipose tissue insulin sensitivity and glucose uptake is controversial. Some studies suggest that H(2)S inhibits insulin-induced glucose uptake and that excess of H(2)S contributes to adipose tissue insulin resistance in metabolic syndrome. In contrast, other studies have demonstrated that H(2)S stimulates glucose uptake and its deficiency contributes to insulin resistance. Similarly, the effect of H(2)S on adipose tissue lipolysis is controversial. H(2)S produced by perivascular adipose tissue decreases vascular tone by activating ATP-sensitive and/or voltage-gated potassium channels in smooth muscle cells. Experimental obesity induced by high calorie diet has a time dependent effect on H(2)S in perivascular adipose tissue; short and long-term obesity increase and decrease H(2)S production, respectively. Hyperglycemia has been consistently demonstrated to suppress CSE-H(2)S pathway in various adipose tissue depots. Finally, H(2)S deficiency may contribute to adipose tissue inflammation associated with obesity/metabolic syndrome.