Astragaloside IV Attenuates Lipolysis and Improves Insulin Resistance Induced by TNFα in 3T3-L1 Adipocytes

Increased circulating free fatty acid (FFA) concentrations have been demonstrated to potentially link obesity, insulin resistance and cardiovascular diseases. Astragaloside IV (AS-IV) is a saponin which is widely used in traditional Chinese medicine to treat type 2 diabetes and cardiovascular diseases. The purpose of the present study was to examine the effects of AS-IV on the lipolysis and insulin resistance induced by tumor necrosis factor-alpha (TNF alpha) in cultured 3T3-L1 adipocytes. TNFa promotes lipolysis in mammal adipocytes via the mitogen activated protein kinase (MAPK) family resulting in reduced expression/function of perilipin. Application of AS-IV inhibited TNF alpha-induced accelerated lipolysis in a dose-dependent manner, which was compatible with suppressed phosphorylation of ERK1/2 and reversed the downregulation of perilipin. Moreover, TNFa induced downregulation of key enzymes in lipogenesis, including LPL, FAS and GPAT, were also attenuated by AS-IV. Further studies showed that AS-IV improved TNFa-induced insulin resistance in 3T3-L1 adipocytes. This study provides the first direct evidence of the antilipolytic action of AS-IV in adipocytes, which may allow this agent to decrease the circulating FFA levels, thus increase insulin sensitivity and treat cardiovascular diseases. Copyright (C) 2008 John Wiley & Sons, Ltd.