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

Abstract 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-α and -β 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-β 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.