PMID- 24993166 OWN - NLM STAT- MEDLINE DCOM- 20150910 LR - 20140811 IS - 1096-0023 (Electronic) IS - 1043-4666 (Linking) VI - 69 IP - 2 DP - 2014 Oct TI - TNF-alpha reduces g0s2 expression and stimulates lipolysis through PPAR-gamma inhibition in 3T3-L1 adipocytes. PG - 196-205 LID - S1043-4666(14)00165-3 [pii] LID - 10.1016/j.cyto.2014.06.005 [doi] AB - Tumor necrosis factor-alpha (TNF-alpha) is a multifunctional cytokine that acts as a mediator of obesity-linked insulin resistance (IR). It is commonly accepted that macrophage-derived TNF-alpha acts in a paracrine manner on adjacent adipocytes, induces lipolysis, which contributes to obesity-linked hyperglycemia. Several studies suggested that G0/G1 switch gene 2 (g0s2) was up-regulated during adipogenesis, and its protein could be degraded in response to TNF-alpha stimulation. The aim of the present work was to investigate the transcriptional regulation of g0s2 by TNF-alpha stimulation. In this study, 3T3-L1 pre-adipocytes were differentiated, and treated with TNF-alpha for 24h. The effects of TNF-alpha on lipolysis and lipase expression were then examined. Our results revealed that TNF-alpha exerted dose- and time-dependent lipolytic effects, which could be partially reversed by overexpression of g0s2 and peroxisome proliferator-activated receptor-gamma (ppar-gamma). In addition, TNF-alpha treatment significantly reduced the expression of adiponectin, ppar-gamma, hormone-sensitive Lipase (hsl), adipose triglyceride lipase (atgl) as well as ATGL co-factors. Interestingly, TNF-alpha significantly decreased adiponectin and PPAR-gamma protein levels, while treatment with the proteasomal inhibitor MG-132 maintained PPAR-gamma levels. Degradation of PPAR-gamma almost completely abolished the binding of PPAR-gamma to the g0s2 promoter in adipocytes treated with TNF-alpha. We propose that proteasomal degradation of PPAR-gamma and the reduction of g0s2 content are permissive for prolonged TNF-alpha induced lipolysis. CI - Copyright (c) 2014 Elsevier Ltd. All rights reserved. FAU - Jin, Dan AU - Jin D AD - Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, PR China. Electronic address: dan.king1983@gmail.com. FAU - Sun, Jun AU - Sun J AD - Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, PR China. FAU - Huang, Jing AU - Huang J AD - Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, PR China. FAU - He, Yiduo AU - He Y AD - Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, PR China. FAU - Yu, An AU - Yu A AD - Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, PR China. FAU - Yu, Xiaoling AU - Yu X AD - Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, PR China. FAU - Yang, Zaiqing AU - Yang Z AD - Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, PR China. Electronic address: yangzq@mail.hzau.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140701 PL - England TA - Cytokine JT - Cytokine JID - 9005353 RN - 0 (Adiponectin) RN - 0 (Cell Cycle Proteins) RN - 0 (G0S2 protein, mouse) RN - 0 (PPAR gamma) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 2.3.1.51 (1-Acylglycerol-3-Phosphate O-Acyltransferase) RN - EC 2.3.1.51 (Abhd5 protein, mouse) RN - EC 3.1.1.3 (Lipase) RN - EC 3.4.25.1 (Proteasome Endopeptidase Complex) RN - PDC6A3C0OX (Glycerol) SB - IM MH - 1-Acylglycerol-3-Phosphate O-Acyltransferase/metabolism MH - 3T3-L1 Cells MH - Adipocytes/drug effects/*metabolism MH - Adiponectin/metabolism MH - Animals MH - Cell Cycle Proteins/*genetics/metabolism MH - Cell Shape/drug effects MH - Down-Regulation/drug effects MH - Glycerol/metabolism MH - Lipase/metabolism MH - Lipolysis/*drug effects/genetics MH - Mice MH - PPAR gamma/*antagonists & inhibitors/metabolism MH - Promoter Regions, Genetic/genetics MH - Proteasome Endopeptidase Complex/drug effects/metabolism MH - Tumor Necrosis Factor-alpha/*pharmacology OTO - NOTNLM OT - Adipocyte OT - G0S2 OT - Lipolysis OT - PPAR-gamma OT - TNF-alpha EDAT- 2014/07/06 06:00 MHDA- 2015/09/12 06:00 CRDT- 2014/07/05 06:00 PHST- 2013/08/12 00:00 [received] PHST- 2014/05/22 00:00 [revised] PHST- 2014/06/04 00:00 [accepted] PHST- 2014/07/05 06:00 [entrez] PHST- 2014/07/06 06:00 [pubmed] PHST- 2015/09/12 06:00 [medline] AID - S1043-4666(14)00165-3 [pii] AID - 10.1016/j.cyto.2014.06.005 [doi] PST - ppublish SO - Cytokine. 2014 Oct;69(2):196-205. doi: 10.1016/j.cyto.2014.06.005. Epub 2014 Jul 1.