Sulfhydration of perilipin 1 is involved in the inhibitory effects of cystathionine gamma lyase/hydrogen sulfide on adipocyte lipolysis
Sulfhydration of perilipin 1 is involved in the inhibitory effects of cystathionine gamma lyase/hydrogen sulfide on adipocyte lipolysis
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Perilipin 1 的硫酸化参与胱硫醚γ裂解酶/硫化氢对脂肪细胞脂肪分解的抑制作用
DOI：
10.1016/j.bbrc.2019.10.192
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发表时间：
2020-01-15
影响因子：
3.1
通讯作者：
Xu, Guoheng
中科院分区：
文献类型：
--
作者：
Ding, Yajun;Wang, Huamin;Xu, Guoheng
硫化氢(H_2S)是一种新的脂肪因子，介导葡萄糖的摄取、脂肪的储存和动员，从而导致肥胖和相关疾病的发生。我们以前的工作表明，H_2S通过减少Perilipin-1(PLIN-1)的磷酸化来抑制异丙肾上腺素刺激的脂解作用，Perilipin-1是一种阻止脂肪酶通路的脂滴蛋白。硫化氢如何调节plin-1的磷酸化仍不清楚。我们目前的研究发现，硫化氢供体略微增加了小鼠的脂肪组织重量，减少了脂肪分解；相比之下，删除脂肪细胞中关键的硫化氢生成酶胱硫醚伽玛裂解酶(CSE)可以降低脂肪积累并促进脂肪分解。有趣的是，一个硫化氢供体诱导了plin-1的硫水化，但不能诱导激素敏感的脂肪酶，并且CSE的缺失取消了plin-1的翻译后修饰。在异丙肾上腺素刺激的脂解过程中，plin-1的硫水化与磷酸化的减少有关，而用二硫苏糖醇去除硫水化可恢复磷酸化。最后，plin-1基因敲除消除了H_2S对脂解的影响，这表明plin-1硫酸盐水合作用是H_2S在脂解中的主要直接靶点。我们已经确定了plin-1的一种新的翻译后修饰，即硫水化(由H_2S直接作用)，导致磷酸化减少，然后减少脂解。这一发现也强调了脂肪分解的一种新的分子调控机制。(C)2019 Elsevier Inc.保留所有权利。
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. (C) 2019 Elsevier Inc. All rights reserved.