title: c-Jun N-terminal kinase is involved in the suppression of adiponectin expression by TNF-alpha in 3T3-L1 adipocytes.
abstract: Adiponectin, one of adipokines that is secreted from adipocytes, plays an important role in the regulation of glucose and lipid metabolism. Paradoxically, serum concentrations of adiponectin are decreased in obese and type 2 diabetic patients, although it is produced in adipose tissue. On the other hand, plasma TNF-alpha levels are increased in such subjects. In the present study, the mechanism by which adiponectin is regulated by TNF-alpha was investigated. The decreased adiponectin mRNA levels by TNF-alpha were partially recovered by treatment with a c-Jun N-terminal kinase (JNK) inhibitor or the PPAR-gamma agonist rosiglitazone in 3T3-L1 adipocytes. Interestingly, however, cotreatment with the JNK inhibitor and rosiglitazone led to a recovery of TNF-alpha-mediated adiponectin suppression to the control level. The JNK inhibitor regulated the expression of adiponectin by the increase of PPAR-gamma DNA binding activity and the recovery of its mRNA expression while rosiglitazone acted via a PPAR-gamma independent pathway which remains to be elucidated. These findings suggest that the JNK signaling pathway, activated by TNF-alpha, is involved in the regulation of adiponectin expression.
authors.affiliation: Laboratory of Immunology, Korea Research Institute of Bioscience and Biotechnology, Daejon 305-333, Republic of Korea.
authors.forename: Kun-yong
authors.initials: KY
authors.lastname: Kim
authors.forename: Jae Kwang
authors.initials: JK
authors.lastname: Kim
authors.forename: Jun Ho
authors.initials: JH
authors.lastname: Jeon
authors.forename: Suk Ran
authors.initials: SR
authors.lastname: Yoon
authors.forename: Inpyo
authors.initials: I
authors.lastname: Choi
authors.forename: Young
authors.initials: Y
authors.lastname: Yang
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D052242:Adiponectin; D000818:Animals; D004247:DNA / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D052242:Adiponectin; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D047495:PPAR gamma; D017382:Reactive Oxygen Species; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; C015482:protein kinase modulator; D000077154:Rosiglitazone; D004247:DNA; D048031:JNK Mitogen-Activated Protein Kinases