Genistein improves liver function and attenuates non-alcoholic fatty liver disease in a rat model of insulin resistance.

The high fructose-fed rat is widely used as a model of insulin resistance. Genistein, a soy isoflavone, has been shown to improve insulin sensitivity in this model. The present study investigated whether genistein could prevent fatty liver disease in this model. Male Wistar rats were fed a diet containing starch (control) or 60% fructose (insulin-resistant model). Fifteen days later, rats in each dietary group were divided into two groups and were treated with either genistein (1 mg/kg per day) in dimethylsulfoxide (DMSO) or 30% DMSO alone. After 60 days, markers of liver injury, oxidative stress, interleukin (IL)-6, tumor necrosis factor (TNF)-α, lipids, lipoprotein profile, nitrite, and nitrosothiol in the plasma and liver were quantified. Liver sections were examined for 3-nitrotyrosine (3-NT) expression and pathological lesions. Fructose-fed rats displayed hyperlipidemia, significant changes in plasma lipoprotein profile, and increases in IL-6 and TNF-α levels compared with control. In addition, the accumulation of lipids, liver injury, a decline in liver function, inactivation of the glyoxalase system, depletion of antioxidants, and increased 3-NT expression were observed in the fructose-fed group. Administration of genistein to fructose-fed rats significantly reduced these biochemical and histological abnormalities. Genistein activates the antioxidant profile, decreases IL-6 and TNF-α concentrations, prevents oxidative damage, and ameliorates fatty liver in insulin-resistant rats. © 2009 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.