Zhi-hong Wu1, Shui-ping Zhao, Luo-xiang Chu, Hui-jun Ye. 1. Department of Cardiology, The Second Xiangya Hospital of Central South University, Middle Ren-Min road No 139, Changsha, Hunan 410011, PR China.
Abstract
BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is an inflammatory cytokine involved in atherogenesis. Adipose tissue is an important source of endogenous TNF-alpha production. Pioglitazone, a member of the thiazolidinediones (TZDs), has anti-inflammatory and anti-atherogenic properties, while underlying mechanism has not been fully elucidated. The aim of this study was to evaluate the effect of pioglitazone on TNF-alpha serum concentration and mRNA expressions of subcutaneous adipose tissue in hypercholesterolemic rabbits. METHODS: Ten rabbits fed with high-cholesterol diet for 8 weeks were randomly divided into two groups: (1) high cholesterol group (n=5): maintained high cholesterol diet for 4 weeks; (2) pioglitazone group (n=5): the same cholesterol diet plus pioglitazone (3 mg/kg/day) for 4 weeks. Control group (n=5) was fed with normal diet for 12 weeks. Subcutaneous adipose tissue was collected for RNA analysis. The direct effect of pioglitazone on TNF-alpha release was assayed in primary rabbit adipocytes. TNF-alpha levels in serum and adipocytes culture supernatant were measured by ELISA. RT-PCR was used to evaluate TNF-alpha mRNA expressions in adipose tissue and adipocytes. RESULTS: Compared with control group, rabbits fed with high cholesterol diet showed significantly higher levels of serum total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and TNF-alpha. Though having no effect on serum glucose level and lipid profile, pioglitazone administration significantly reduced circulating TNF-alpha concentrations, which were positively correlated with TNF-alpha mRNA expressions of adipose tissue (r=0.53, P<0.01). Pioglitazone dose-dependently inhibited lipopolysaccharide (LPS)-induced TNF-alpha secretion and mRNA expression in cultured adipocytes. CONCLUSION: Pioglitazone significantly reduced serum TNF-alpha level in hypercholesterolemic rabbits independent of its metabolic actions, which may at least partly be due to its direct inhibition of TNF-alpha expression and secretion of adipocytes. This may help to explain the mechanism by which pioglitazone exert anti-atherosclerotic effects. Copyright (c) 2008 Elsevier Ireland Ltd. All rights reserved.
BACKGROUND:Tumor necrosis factor-alpha (TNF-alpha) is an inflammatory cytokine involved in atherogenesis. Adipose tissue is an important source of endogenous TNF-alpha production. Pioglitazone, a member of the thiazolidinediones (TZDs), has anti-inflammatory and anti-atherogenic properties, while underlying mechanism has not been fully elucidated. The aim of this study was to evaluate the effect of pioglitazone on TNF-alpha serum concentration and mRNA expressions of subcutaneous adipose tissue in hypercholesterolemic rabbits. METHODS: Ten rabbits fed with high-cholesterol diet for 8 weeks were randomly divided into two groups: (1) high cholesterol group (n=5): maintained high cholesterol diet for 4 weeks; (2) pioglitazone group (n=5): the same cholesterol diet plus pioglitazone (3 mg/kg/day) for 4 weeks. Control group (n=5) was fed with normal diet for 12 weeks. Subcutaneous adipose tissue was collected for RNA analysis. The direct effect of pioglitazone on TNF-alpha release was assayed in primary rabbit adipocytes. TNF-alpha levels in serum and adipocytes culture supernatant were measured by ELISA. RT-PCR was used to evaluate TNF-alpha mRNA expressions in adipose tissue and adipocytes. RESULTS: Compared with control group, rabbits fed with high cholesterol diet showed significantly higher levels of serum total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and TNF-alpha. Though having no effect on serum glucose level and lipid profile, pioglitazone administration significantly reduced circulating TNF-alpha concentrations, which were positively correlated with TNF-alpha mRNA expressions of adipose tissue (r=0.53, P<0.01). Pioglitazone dose-dependently inhibited lipopolysaccharide (LPS)-induced TNF-alpha secretion and mRNA expression in cultured adipocytes. CONCLUSION:Pioglitazone significantly reduced serum TNF-alpha level in hypercholesterolemic rabbits independent of its metabolic actions, which may at least partly be due to its direct inhibition of TNF-alpha expression and secretion of adipocytes. This may help to explain the mechanism by which pioglitazone exert anti-atherosclerotic effects. Copyright (c) 2008 Elsevier Ireland Ltd. All rights reserved.
Authors: Valentina Spigoni; Angela Picconi; Monia Cito; Valentina Ridolfi; Sabrina Bonomini; Chiara Casali; Ivana Zavaroni; Luigi Gnudi; Marco Metra; Alessandra Dei Cas Journal: PLoS One Date: 2012-11-05 Impact factor: 3.240