title: GO6976 prevents TNF-alpha-induced suppression of adiponectin expression in 3T3-L1 adipocytes: putative involvement of protein kinase C.
abstract: Adiponectin, one of the adipokines secreted by adipocytes, possesses insulin sensitizing and anti-atherosclerotic properties. Tumor necrosis factor-alpha (TNF-alpha) is known to suppress the expression and secretion of adiponectin in adipocytes; however, the underlying mechanism remains poorly understood. Here, we demonstrate that GO6976 (a selective inhibitor of conventional protein kinase C (PKC)) prevents TNF-alpha-induced suppression of adiponectin secretion and expression in fully differentiated 3T3-L1 adipocytes, accompanied by attenuation of c-Jun N-terminal kinase (JNK) activation. Additionally, the transcriptional activity of peroxisome proliferator-activated receptor-gamma (PPARg) (a strong inducer of adiponectin) on the adiponectin promoter was inhibited in a PKC isoform-specific manner. These results raise the possibility that PKC is involved in TNF-alpha-induced suppression of adiponectin in 3T3-L1 adipocytes.
authors.affiliation: Division of Intractable Diseases, Center for Biomedical Sciences, National Institute of Health, 194 Tongillo, Eunpyeong-gu, Seoul 122-701, Republic of Korea.
authors.forename: Joong-Yeon
authors.initials: JY
authors.lastname: Lim
authors.forename: Won Ho
authors.initials: WH
authors.lastname: Kim
authors.forename: Sang Ick
authors.initials: SI
authors.lastname: Park
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D052242:Adiponectin / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051379:Mice; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D002227:Carbazoles; D007527:Isoenzymes; D047495:PPAR gamma; D047428:Protein Kinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; C081021:Go 6976; D011493:Protein Kinase C; D048031:JNK Mitogen-Activated Protein Kinases