title: Cytoplasmic receptor-interacting protein 140 (RIP140) interacts with perilipin to regulate lipolysis.
abstract: 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.
authors.affiliation: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
authors.forename: Ping-Chih
authors.initials: PC
authors.lastname: Ho
authors.forename: Ya-Shan
authors.initials: YS
authors.lastname: Chuang
authors.forename: Chen-Hsiang
authors.initials: CH
authors.lastname: Hung
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Wei
mesh_terms: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase / Q000378:metabolism; D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins; D008049:Lipase / Q000378:metabolism; D008066:Lipolysis / Q000502:physiology*; D008297:Male; D008745:Methylation; D051379:Mice; D008810:Mice, Inbred C57BL; D056971:Nuclear Receptor Co-Repressor 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D051744:Protein Kinase C-epsilon / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D002787:Sterol Esterase / Q000378:metabolism; D000217:Acyltransferases
chemical_list: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; D002352:Carrier Proteins; D008049:Lipase; D056971:Nuclear Receptor Co-Repressor 1; D000070778:Perilipin-1; D010750:Phosphoproteins; D051744:Protein Kinase C-epsilon; D034741:RNA, Small Interfering; D002787:Sterol Esterase; C492986:Abhd5 protein, mouse; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases