Increase or decrease hydrogen sulfide exert opposite lipolysis, but reduce global insulin resistance in high fatty diet induced obese mice.
Increase or decrease hydrogen sulfide exert opposite lipolysis, but reduce global insulin resistance in high fatty diet induced obese mice.
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增加或减少硫化氢会产生相反的脂肪分解作用，但会降低高脂肪饮食诱导的肥胖小鼠的整体胰岛素抵抗
DOI：
10.1371/journal.pone.0073892
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Xu GH
中科院分区：
文献类型：
--
作者：
Geng B;Cai B;Liao F;Zheng Y;Zeng Q;Fan X;Gong Y;Yang J;Cui QH;Tang C;Xu GH
目的脂肪组织表达内源性半胱硫氨酸伽马裂解酶(CSE)/硫化氢(H 2S)系统。硫化氢前体抑制儿茶酚胺刺激的脂解反应。因此，我们推测CSE/H_2S系统调节脂解作用，从而导致胰岛素抵抗的发生。方法大鼠脂肪细胞分别用L-丙叉甘氨酸、硫代前体L-半胱氨酸+磷酸吡哆醇(辅酶)或硫氢缓释供体GYY4137处理，然后测定甘油水平以评估脂肪细胞的脂解作用。观察PAG和GYY4137对高脂饮食诱导的肥胖小鼠胰岛素抵抗的影响。结果在这里，我们发现PAG呈时间依赖性地增加基础或异丙肾上腺素刺激的脂解。而L-半胱氨酸+磷酸吡哆醇或GYY4137则显著降低其活性。PAG使磷酸化蛋白激酶A底物、Perilipin-1和激素敏感脂肪酶升高，而L-半胱氨酸和GYY4137则降低这些参数。在HFD诱导的肥胖小鼠中，PAG增加脂肪基础脂解，从而钝化脂肪质量的增加，从而降低胰岛素抵抗，表现为降低空腹血糖、胰岛素水平、HOMA指数、口服葡萄糖耐量试验(OGTT)曲线面积和提高胰岛素耐量试验(ITT)反应。GYY4137在体内抑制脂肪分解而不增加脂肪质量，但也改善了HFD小鼠的胰岛素抵抗。结论抑制脂肪细胞内源性CSE/H 2S系统可通过蛋白激酶A-Perilipin/激素敏感型脂肪酶途径增加脂肪分解，从而钝化肥胖小鼠的脂肪量增加，降低胰岛素抵抗；给予H 2S供体可减少脂肪分解，也可减轻高脂饮食诱导的胰岛素抵抗。我们的数据显示，增加或减少硫化氢引起相反的脂解，但对胰岛素抵抗有相同的影响。这种矛盾的调节可能是由于H_2S对脂肪细胞代谢和内分泌功能的不同作用所致。
Objective Adipose tissue expressed endogenous cystathionine gamma lyase (CSE)/hydrogen sulfide (H2S) system. H2S precursor inhibited catecholamine stimulated lipolysis. Thus, we hypothesized that CSE/H2S 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 H2S precursor) plus pyridoxial phosphate (co-enzyme) or the H2S 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/H2S 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 H2S donor decreased lipolysis, also reduced insulin resistance induced by HFD. Our data showed that increase or decrease H2S induced opposite lipolysis, but had the same effect on insulin resistance. The paradoxical regulation may be resulted from different action of H2S on metabolic and endocrine function in adipocyte.
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影响因子：
2.2
作者：
Kawasaki, Masashi;Miura, Yutaka;Yagasaki, Kazumi
通讯作者：
Yagasaki, Kazumi
DOI：
10.1111/j.1749-6632.1999.tb07794.x
发表时间：
1999-01-01
期刊：
THE METABOLIC SYNDROME X
影响因子：
--
作者：
Londos, C;Brasaemle, DL;Rondinone, CM
通讯作者：
Rondinone, CM
影响因子：
7.1
作者：
Elshorbagy, Amany K.;Nurk, Eha;Refsum, Helga
通讯作者：
Refsum, Helga
影响因子：
13.6
作者：
Lass, Achim;Zimmermann, Robert;Oberer, Monika;Zechner, Rudolf
通讯作者：
Zechner, Rudolf
影响因子：
5.3
作者：
Dhawan, Saurabh S.;Eshtehardi, Parham;Samady, Habib
通讯作者：
Samady, Habib