• Sujong Kim, Insuk Sohn, Yeon Sook Lee, and Yong Sung Lee.
• Department of Biochemistry, College of Medicine, Hanyang University, Seoul 133-791, Korea.
• J. Nutr. 2005 Jan 1; 135 (1): 33-41.

AbstractWe reported previously that genistein enhances the expression of genes involved in fatty acid catabolism through activation of peroxisome proliferator-activated receptor (PPAR) alpha in HepG2 cells, suggesting that genistein holds great promise for therapeutic applications to lipid abnormalities such as obesity and hyperlipidemia in humans. In this study, we examined the changes in hepatic transcriptional profiles using cDNA microarrays in mice with high-fat diet (HFD)-induced obesity supplemented with genistein. C57BL/6J male mice (n = 10/group) were fed a low-fat diet (LFD), a HFD, or a HFD supplemented with 2 g/kg genistein (HFD+GEN) for 12 wk. Mice fed the HFD had abnormal lipid profiles and significantly greater body weight and visceral fat accumulation than the LFD-fed group. Genistein supplementation improved lipid profiles and hepatic steatosis and attenuated the increases in body weight and visceral fat in HFD-fed mice. The cDNA microarrays revealed marked alterations in the expression of 107 genes in the mice fed the HFD and/or the HFD+GEN. Of 97 transcripts altered in the HFD-fed group, 84 genes were normalized by genistein supplementation. However, several genes involved in fatty acid catabolism were not normalized but were still upregulated in the HFD+GEN-fed group, relative to the LFD-fed group. Furthermore, carnitine O-octanoyltransferase, which accelerates fatty acid oxidation, was not affected by the HFD, but was induced by genistein supplementation. These results are consistent with our previous study showing that genistein is an activator of PPAR alpha in vitro. This study showed beneficial effects of genistein supplementation in preventing the development of obesity and metabolic abnormalities in mice with diet-induced obesity. Our results also provide interesting information about the genes associated with the beneficial effects of genistein as well as the mechanisms underlying the development and maintenance of the obesity phenotype in vivo.

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