Adipocytes behave as a rich source of pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha) and monocyte chemoattractant protein 1 (MCP-1). Endoplasmic reticulum (ER) stress in adipocytes can alter adipokines secretion and induce inflammation. The aim of this study is to evaluate the effect of simvastatin on the ox-LDL-induced ER stress and expression and secretion of TNF-alpha and MCP-1 in 3T3-L1 adipocytes. Differentiated adipocytes were treated with various concentrations of ox-LDL (0-100 mu g/ml) for 24 h with or without simvastatin pre-treatment. The protein expressions of ER stress markers, glucose-regulated protein 78 (GRP78) and C/EBP homology protein (CHOP), were determined by Western blot analysis. The mRNA expressions of TNF-alpha. and MCP-1 were measured by real-time PCR. The protein release of TNF-alpha and MCP-1 in culture medium were evaluated by ELISA. Ox-LDL treatment led to significant up-regulation of GRP78 and CHOP in dose-dependent manner. The expressions of TNF-alpha and MCP-1 were dose-dependently increased at mRNA and protein levels after ox-LDL intervention. The effects of ox-LDL on adipocytes were abolished by pre-treatment with 4-phenylbutyrate (4-PBA), a chemical chaperone known to ameliorate ER stress. Simvastatin could inhibit ox-LDL-induced ER stress and reduce the expression of TNF-alpha and MCP-1 at mRNA and protien level in dose dependent manner. In conclusion, ox-LDL can stimulate the expression and secretion of TNF-alpha. and MCP-1 through its activation of ER stress in adipocytes. Simvastatin might exert direct anti-inflammatory effects in adipocytes through amelioration of ER stress. (C) 2013 Elsevier Inc. All rights reserved.