Dietary Soy Protein Isolate Modifies Hepatic Retinoic Acid Receptor-b Proteins and Inhibits Their DNA Binding Activity in Rats

Retinoic acid receptors (RAR) belong to the same nuclear receptor superfamily as thyroid hormone receptors (TR) that were previously shown to be modulated by dietary soy protein isolate (SPI). This study has examined the effect of dietary SPI and isoflavones (ISF) on hepatic RAR gene expression and DNA binding activity. In Expt. 1, Sprague-Dawley rats were fed diets containing 20% casein or 20% alcohol-washed SPI in the absence or presence of increasing amounts of ISF (5– 1250 mg/kg diet) for 70, 190, or 310 d. In Expt. 2, weanling Sprague-Dawley rats were fed diets containing 20% casein with or without supplemental ISF (50 mg/kg diet) or increasing amounts of alcohol-washed SPI (5, 10, and 20%) for 90 d. Intake of soy proteins significantly elevated hepatic RARb2 protein content dose-dependently compared with a casein diet, whereas supplemental ISF had no consistent effect. Neither RARb protein in the other tissues measured nor the other RAR (RARa and RARg) in the liver were affected by dietary SPI, indicating a tissue and isoform-specific effect of SPI. RARb2 mRNA abundances were not different between dietary groups except that its expression was markedly suppressed in male rats fed SPI for 310 d. DNA binding activity of nuclear RARb was significantly attenuated and the isoelectric points of RARb2 were shifted by dietary SPI. Overall, these results show for the first time, to our knowledge, that dietary soy proteins affect hepatic RARb2 protein content and RARb DNA binding activity, which may contribute to the suppression of retinoid-induced hypertriglyceridemia by SPI as reported. J. Nutr. 137: 1–6, 2007.