Genistein reduced insulin resistance index through modulating lipid metabolism in ovariectomized rats

Nov 27, 2012Nutrition research (New York, N.Y.)

Genistein lowers insulin resistance by changing fat metabolism in rats without ovaries

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Abstract

Ovariectomized rats showed a reduction in insulin resistance index with 0.1% genistein supplementation.

Ovariectomized rats experienced increased body weight and insulin resistance compared to sham rats.
Supplemental genistein reduced the insulin resistance index and activity of hepatic fatty acid synthetase.
Genistein treatment was associated with enhanced activity of key enzymes involved in fat metabolism.
Rats receiving genistein exhibited smaller-sized fat cells.
Gene expression analysis revealed that genistein reversed changes in pathways related to fatty acid metabolism and oxidative stress.

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Postmenopausal women are at higher risk for obesity and insulin resistance due to the decline of estrogen, but genistein, a phytoestrogen, may reduce the risks of these diet-related diseases. In this study, we hypothesized that supplemental genistein has beneficial effects on insulin resistance in an ovariectomized rat model by modulating lipid metabolism. Three weeks after a sham surgery (sham) or an ovariectomy (OVX), ovariectomized Sprague-Dawley rats were placed on a diet containing 0 (OVX group) or 0.1% genistein for 4 weeks. The sham rats were fed a high-fat diet containing 0% genistein and served as the control group (sham group). The ovariectomized rats showed increases in body weight and insulin resistance index, but genistein reduced insulin resistance index and the activity of hepatic fatty acid synthetase. Genistein was also associated with increased activity of succinate dehydrogenase and carnitine palmitoyltransferase and the rate of β-oxidation in the fat tissue of rats. The ovariectomized rats given genistein had smaller-sized adipocytes. Using gene-set enrichment analysis (GSEA) of microarray data, we found that a number of gene sets of fatty acid metabolism, insulin resistance, and oxidative stress were differentially expressed by OVX and reversed by genistein. This systemic approach of GSEA enables the identification of such consensus between the gene expression changes and phenotypic changes caused by OVX and genistein supplementation. Genistein treatment could help reduce insulin resistance through the amelioration of OVX-induced metabolic dysfunction, and the GSEA approach may be useful in proposing putative targets related to insulin resistance.

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Genistein reduced insulin resistance index through modulating lipid metabolism in ovariectomized rats

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