In:
American Journal of Physiology-Endocrinology and Metabolism, American Physiological Society, Vol. 294, No. 5 ( 2008-05), p. E898-E909
Abstract:
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-α (TNF-α; 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-α 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 IκB phosphorylation inhibitors BAY 11-7085 and BMS-345541 ( P 〈 0.01). MCP-1 secretion was not affected by peroxisome proliferator-activated receptor-γ (PPARγ) 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-α and IL-1β as well as by PPARγ antagonists bisphenol A diglycidyl ether and T0070907 ( P 〈 0.01). JNK inhibitors and IκB 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 IκB signaling. In contrast, the parallel increase in adiponectin expression appears to be related to the PPARγ ligand properties of palmitate.
Type of Medium:
Online Resource
ISSN:
0193-1849
,
1522-1555
DOI:
10.1152/ajpendo.00131.2007
Language:
English
Publisher:
American Physiological Society
Publication Date:
2008
detail.hit.zdb_id:
1477331-4
SSG:
12
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