Cytoplasmic receptor-interacting protein 140 (RIP140) interacts with perilipin to regulate lipolysis.
Cytoplasmic receptor-interacting protein 140 (RIP140) interacts with perilipin to regulate lipolysis.
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DOI：
10.1016/j.cellsig.2011.03.023
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发表时间：
2011-08
影响因子：
4.8
通讯作者：
Wei LN
中科院分区：
文献类型：
--
作者：
Ho PC;Chuang YS;Hung CH;Wei LN
受体相互作用蛋白140(RIP140)在成熟脂肪细胞中大量表达，调节与脂肪和糖代谢相关的基因表达。蛋白激酶C epsilon和蛋白精氨酸甲基转移酶1可以依次刺激RIP140的磷酸化，然后甲基化，从而促进其输出到细胞质。在这里，我们报道了一种触发RIP140胞浆积聚的脂质信号，以及胞浆RIP140在脂肪细胞中调节脂解的新功能。脂质含量的增加，特别是二酰甘油水平的增加，通过与Perilipin的直接相互作用，促进了RIP140在细胞质中的积累，并增加了与脂滴(LDS)的结合。通过与RIP140相互作用，Perilipin更有效地将激素敏感脂肪酶(HSL)招募到LDS，并增强脂肪甘油三酯脂肪酶(ATGL)与ATGL激活剂CGI-58形成复合体。因此，HSL可以更容易地接触到它的底物，ATGL被激活，最终加强脂解。在脂肪细胞中，阻断胞浆中RIP140的积聚可以减少基础和异丙肾上腺素刺激的脂解作用及其条件培养液的促炎潜力(即激活巨噬细胞中的核因子-κB和炎症基因)。这些结果表明，在高脂含量的脂肪细胞中，RIP140通过直接与Perilipin相互作用，增加在细胞质中的积聚，并增强甘油三酯的分解代谢。这项研究表明，减少RIP140的核输出可能是控制脂肪细胞脂解的有效手段。
Receptor-interacting protein 140 (RIP140) is abundantly expressed in mature adipocyte and modulates gene expression involved in lipid and glucose metabolism. Protein kinase C epsilon and protein arginine methyltransferase 1 can sequentially stimulate RIP140 phosphorylation and then methylation, thereby promoting its export to the cytoplasm. Here we report a lipid signal triggering cytoplasmic accumulation of RIP140, and a new functional role for cytoplasmic RIP140 in adipocyte to regulate lipolysis. Increased lipid content, particularly an elevation in diacylglycerol levels, promotes RIP140 cytoplasmic accumulation and increased association with lipid droplets (LDs) by its direct interaction with perilipin. By interacting with RIP140, perilipin more efficiently recruits hormone-sensitive lipase (HSL) to LDs and enhances adipose triglyceride lipase (ATGL) forming complex with CGI-58, an activator of ATGL. Consequentially, HSL can more readily access its substrates, and ATGL is activated, ultimately enhancing lipolysis. In adipocytes, blocking cytoplasmic RIP140 accumulation reduces basal and isoproterenol-stimulated lipolysis and the pro-inflammatory potential of their conditioned media (i.e. activating NF-κB and inflammatory genes in macrophages). These results show that in adipocytes with high lipid contents, RIP140 increasingly accumulates in the cytoplasm and enhances triglyceride catabolism by directly interacting with perilipin. The study suggests that reducing nuclear export of RIP140 might be a useful means of controlling adipocyte lipolysis.
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