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Objective  Adipose tissue expressed endogenous cystathionine gamma lyase (CSE)/hydrogen sulfide (H 2 S) system. H 2 S precursor inhibited catecholamine stimulated lipolysis. Thus, we hypothesized that CSE/H 2 S system regulates lipolysis which contributed to the pathogenesis of insulin resistance.    Methods  We treated rat adipocyte with DL-propargylglycine (PAG, a CSE inhibitor), L-cysteine (an H 2 S precursor) plus pyridoxial phosphate (co-enzyme) or the H 2 S chronic release donor GYY4137, then the glycerol level was assayed for assessing the lipolysis. Then, the effects of PAG and GYY4137 on insulin resistance in high fatty diet (HFD) induced obese mice were investigated.    Results  Here, we found that PAG time-dependently increased basal or isoproterenol stimulated lipolysis. However, L-cysteine plus pyridoxial phosphate or GYY4137 significantly reduced it. PAG increased phosphorylated protein kinase A substrate, perilipin 1 and hormone sensitive lipase, but L-cysteine and GYY4137 decreased the parameters. In HFD induced obese mice, PAG increased adipose basal lipolysis, thus blunted fat mass increase, resulting in lowering insulin resistance evidenced by reduction of fasting glucose, insulin level, HOMA index, oral glucose tolerance test (OGTT) curve area and elevating the insulin tolerance test (ITT) response. GYY4137 inhibited lipolysis in vivo without increasing fat mass, but also ameliorated the insulin resistance in HFD mice.    Conclusion  These results implicated that inhibition endogenous CSE/H 2 S system in adipocytes increased lipolysis by a protein kinase A-perilipin/hormone-sensitive lipase pathway, thus blunted fat mass increase and reduced insulin resistance in obese mice; giving H 2 S donor decreased lipolysis, also reduced insulin resistance induced by HFD. Our data showed that increase or decrease H 2 S induced opposite lipolysis, but had the same effect on insulin resistance. The paradoxical regulation may be resulted from different action of H 2 S on metabolic and endocrine function in adipocyte.

Increase or Decrease Hydrogen Sulfide Exert Opposite Lipolysis, but Reduce Global Insulin Resistance in High Fatty Diet Induced Obese Mice