title: Restoration of adiponectin expression via the ERK pathway in TNFα-treated 3T3-L1 adipocytes.
abstract: Adiponectin and tumor necrosis factor‑α (TNF‑α) exert opposite effects on obesity‑associated inflammation and insulin signaling. The purpose of the present study was to investigate the effects of chronic TNF‑α on adiponectin levels in 3T3‑L1 adipocytes, as well as the potential reversal mechanisms. Differentiated 3T3‑L1 adipocytes were exposed to TNF‑α for three different incubation times and then to various wash‑off periods with or without mitogen‑activated protein kinase (MAPK) inhibitors. TNF‑α significantly reduced adiponectin gene expression in a dose‑ and time‑dependent manner and activated c‑Jun N‑terminal kinases (JNK), extracellular signal‑regulated kinases (ERK) and p38 MAPK. A 16 h restoration period fully reversed the decrease in adiponectin levels following 16 h treatment with TNF‑α; however, 16 h withdrawal of TNF‑α following 32 or 48 h treatment did not completely reverse the TNF‑α‑induced decrease in adiponectin levels. In 3T3‑L1 adipocytes, 32 or 48 h wash‑off periods were required following 32 or 48 h TNF‑α treatments, respectively. The pattern of ERK activation following TNF‑α exposure and removal was similar to the pattern of adiponectin expression. Furthermore, ERK1/2 inhibition accelerated the recovery of adiponectin levels compared with the levels in the untreated control adipocytes. Therefore, the inhibitory effects of TNF‑α on adiponectin levels in differentiated 3T3‑L1 cells were fully reversed following a wash‑out period equivalent to the TNF‑α treatment time, potentially through the ERK 1/2 pathway.
authors.affiliation: Diabetes Research Institute, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 110-746, Korea.
authors.forename: Eugene
authors.initials: E
authors.lastname: Chang
authors.affiliation: Diabetes Research Institute, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 110-746, Korea.
authors.forename: Jung Mook
authors.initials: JM
authors.lastname: Choi
authors.affiliation: Department of Endocrinology and Metabolism, Gangneung Asan Hospital, Ulsan University School of Medicine, Gangneung 201-711, Korea.
authors.forename: Won Jun
authors.initials: WJ
authors.lastname: Kim
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 110-746, Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Rhee
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 110-746, Korea.
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Oh
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 110-746, Korea.
authors.forename: Won-Young
authors.initials: WY
authors.lastname: Lee
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 110-746, Korea.
authors.forename: Se Eun
authors.initials: SE
authors.lastname: Park
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 110-746, Korea.
authors.forename: Sung Woo
authors.initials: SW
authors.lastname: Park
authors.affiliation: Diabetes Research Institute, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 110-746, Korea.
authors.forename: Cheol-Young
authors.initials: CY
authors.lastname: Park
mesh_terms: D041721:3T3-L1 Cells; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D052242:Adiponectin; D005419:Flavonoids; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one