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The Soy Isoflavones Genistein and Daidzein Produce Different Metabolic Effects in Wild‐Type and PPAR‐Alpha KO Mice

Diets containing soy protein have been shown to positively affect several metabolic parameters, the most notable example being serum cholesterol. Isoflavones are one component of soy which have been suggested to be a bioactive component. Recently, isoflavones have been shown to activate the peroxisome‐proliferator activated (PPARs). To evaluate the relative effects of individual isoflavones, wild‐type and PPARa knockout (KO) mice were fed one of four high fat soy protein‐based diets: low‐isoflavone soy protein (S), S supplemented with either 0.3% (w/w) genistein (S+G) or 0.3% (w/w) daidzein (S+D), or soy protein containing a 0.3% (w/w) mixture of isoflavones (S+I). After 4 weeks of feeding, mice were killed and metabolic parameters measured. Overall, the S+G and S+I diets were more effective in producing lipid‐regulating responses, while the S and S+D diets were less effective. Intake of S+G increased liver weight. Serum triglycerides were elevated in mice fed S+D; this was not observed in mice fed other diets. Serum cholesterol levels were decreased in wt mice fed S+G diets and in female mice fed S+I. Intake of S+D did not reduce cholesterol levels. In KO mice, intake of S+D increased serum cholesterol. This was not observed in S+G‐fed wt mice. Our study demonstrates that intake of G and D produce different metabolic effects and sex and presence of PPARa influence the effect of isoflavones on lipid metabolism.