Intake of Genistein and Daidzein Ameliorates Adiposity and Metabolic Syndrome in High Fat Fed C57BL/6J Mice

Genistein and daidzein are isoflavones abundant in soybean. These isoflavones have been shown to have a weak but significant estrogenic effect and other studies have shown isoflavones may impact cancer and metabolic disease. Our prior research (Luo et al. 2014) indicated metabolic improvements in male mice fed a high‐fat (HF) diet supplemented with Novasoy, a dietary supplement containing a mixture of soy isoflavones. With two related, but slightly different chemical structures, it is plausible that dietary genistein and daidzein influence metabolism differently. Objective The objective of the present study was to determine if diet supplementation with genistein (G) or daidzein (D) would have a differential impact on body weight, body composition, and other physiologic and metabolic parameters in high‐fat fed male C57BL/6J mice. Methods C57BL/6J mice (n=8 per group) were provided either low‐fat diet (LF, 10% kcal fat), high‐fat diet (HF, 45% kcal fat), or HF plus ~0.2% of either G or D for 10 weeks. Dietary levels of isoflavones are equivalent to intake of dietary supplements in humans. Body weight was recorded weekly and food intake bi‐weekly. Results Dietary supplementation with G or D led to decreased body weight compared to HF‐fed mice. Furthermore, body weight gain in G‐fed mice was profoundly impacted and lower in value vs. all groups including LF‐fed mice, weight gains were as follows: LF: 7.0 ± 0.6 g, HF: 18.6 ± 1.0 g, G: 2.9 ± 0.7 g, D: 11.9 ± 1.4 g. In glucose tolerance testing, both G and D intake were associated with a trend of decreased area under the curve (AUC), consistent with improved glucose sensitivity vs. HF‐fed mice. Serum insulin levels were consistent with this finding, with concentrations in G‐fed mice significantly lower than HF‐fed and equivalent to LF‐fed mice (P < 0.01). Serum resistin concentrations showed a trend of lower levels vs. HF‐fed mice in G‐ and D‐fed mice (P < 0.01). Serum MCP‐1 levels were measured by ELISA and G‐fed mice had trended to lower MCP‐1 levels compared to HF‐ and D‐fed mice (P < 0.10). Liver tissue sections were evaluated for fat content and relative fat content was LF: 9.0 ± 1.7 %, HF: 30.8 ± 3.8 %, G: 15 ± 3.7 %, D: 30 ± 6.3 %. Hepatic gene expression levels were measured by RT‐PCR, and G‐fed mice had higher levels of several genes related to lipid metabolism including stearoyl‐CoA desaturase‐1 and sterol regulatory element‐binding protein 1a. Conclusion The profound impact of genistein intake on weight gain was unanticipated and needs to be further explored to determine if it may be of use as a dietary supplement to help promote weight loss or to help improve glucose sensitivity. Support or Funding Information Oregon Agricultural Experiment Station