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This Article Full Text Full Text (PDF) All Versions of this Article: 294/5/E898    most recent 00131.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Takahashi, K. Articles by Ishida, H. Search for Related Content PubMed PubMed Citation Articles by Takahashi, K. Articles by Ishida, H.

JNK- and IB-dependent pathways regulate MCP-1 but not adiponectin release from artificially hypertrophied 3T3-L1 adipocytes preloaded with palmitate in vitro

¹Third Department of Internal Medicine, ²Department of Molecular Predictive Medicine and Sport Science, and ³Department of Biochemistry, Kyorin University School of Medicine, Tokyo, Japan

Submitted 26 February 2007 ; accepted in final form 12 February 2008

Obese conditions increase the expression of adipocytokine monocyte chemoattractant protein-1 (MCP-1) in adipose tissue as well as MCP-1 plasma levels. To investigate the mechanism behind increased MCP-1, we used a model in which 3T3-L1 adipocytes were artificially hypertrophied by preloading with palmitate in vitro. As observed in obesity, under our model conditions, palmitate-preloaded cells showed significantly increased oxidative stress and increased MCP-1 expression relative to control cells. This increased MCP-1 expression was enhanced by adding exogenous tumor necrosis factor- (TNF-; 17.8-fold vs. control cells, P < 0.01) rather than interleukin-1β (IL-1β; 2.6-fold vs. control cells, P < 0.01). However, endogenous TNF- and IL-1β release was not affected in hypertrophied cells, suggesting that these endogenous cytokines do not mediate hypertrophy-induced increase in MCP-1. MCP-1 secretion from hypertrophied cells was significantly decreased by treatment with antioxidant N-acetyl-cysteine, JNK inhibitors SP600125 and JIP-1 peptide, and IB phosphorylation inhibitors BAY 11-7085 and BMS-345541 (P < 0.01). MCP-1 secretion was not affected by peroxisome proliferator-activated receptor- (PPAR) antagonists assayed. Adiponectin, another adipocytokine studied in parallel, also showed increased release in hypertrophy relative to control cells. But in contrast to MCP-1, adiponectin release was significantly suppressed by both exogenous TNF- and IL-1β as well as by PPAR antagonists bisphenol A diglycidyl ether and T0070907 (P < 0.01). JNK inhibitors and IB phosphorylation inhibitors showed no significant effect on adiponectin. We conclude that adipocyte hypertrophy through palmitate loading causes oxidative stress, which in turn increases MCP-1 expression and secretion through JNK and IB signaling. In contrast, the parallel increase in adiponectin expression appears to be related to the PPAR ligand properties of palmitate.

c-Jun NH₂-terminal kinase; monocyte chemoattractant protein-1; tumor necrosis factor-; interleukin-1β

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