Effect of genistein on insulin resistance, renal lipid metabolism, and antioxidative activities in ovariectomized rats

Objectives: Postmenopausal women develop obesity, insulin resistance, and potentially renal dysfunction because of decreased serum estrogen levels. We investigated the effects of genistein, an estrogen-like compound thought to exert antioxidative effects, on insulin resistance, renal lipid accumulation, and oxidative stress in ovariectomized rats. Methods: Three weeks after an ovariectomy or a sham surgery, rats were put on a high-fat diet containing 0% or 0.1% genistein for 4 wk. We examined the following treatment groups: sham surgery + high-fat diet (sham), ovariectomy + high-fat diet (OVX), and ovariectomy + high-fat diet with 0.1% genistein (OVX + G). Results: The OVX + G group had increased serum estradiol levels and renal expression of estrogen receptors-alpha and -beta compared with the OVX group. OVX + G rats showed decreases in serum insulin levels and the insulin resistance index. OVX + G rats also exhibited decreased renal triacylglycerol and cholesterol levels, which may have been the result of decreased sterol response element binding protein-1 and -2 expressions, and increased adenosine triphosphate-binding cassette transporter-1 and adiponectin receptor expression. The observed increases in renal lipid levels and serum and renal transforming growth factor-beta in OVX rats may be associated with the increased expression of extracellular matrix proteins, such as fibronectin, and the decreased activity of metalloproteinase-2, an extracellular matrix-degrading enzyme. Ovariectomy also induced oxidative stress by the reduction of antioxidative enzymes, whereas genistein reversed these detrimental ovariectomy-induced effects. Conclusion: Genistein may help to maintain normal kidney function through the alleviation of many ovariectomy-induced risk factors for renal damage, including an increased insulin resistance index, renal oxidative stress, lipid accumulation, and extracellular matrix protein expression. (c) 2009 Published by Elsevier Inc.