Effects of low‐ and high‐ isoflavone soy protein‐based diets on cholesterol metabolism and enterohepatic bile salt recirculation in mice

Abstract

Mice consuming a high-isoflavone containing soy protein diet (HIS) for six weeks had dramatic changes in hepatic and intestinal mRNA expression of genes involved in the cholesterol catabolism and bile acid synthesis pathway as compared to mice consuming a low-isoflavone containing soy protein diet (LIS). Diets were atherogenic, containing 35% of calories from fat and 1.25% cholesterol. In particular, hepatic mRNA levels of cholesterol 7-alpha hydroxylase (cyp7a1), the rate-limiting enzyme for conversion of cholesterol to bile acid, were increased approximately 9-fold in HIS-fed mice. The mRNA levels of other genes in the biliary pathway were moderately increased in HIS- vs. LIS-fed mice, including oxysterol 7-alpha hydroxylase (cyp7b1), sterol 12-alpha hydroxylase (cyp8b1) and cholesterol 27 hydroxylase (cyp27a1). Concurrently, the mRNA levels of the ileal apical sodium-dependent bile acid transporter (asbt or slc10a2) were reduced in both liver and intestinal samples (approximately 55% reduction in both). The Asbt transporter is responsible for the reabsorption of bile salts from the intestine back into the bloodstream for hepatic uptake. Mice consuming the HIS diet also had reduced serum total bile acid levels as compared to LIS-consuming mice. These data provide support at the molecular level for the hypothesis explaining the hypocholesterolemic effect of soy intake through increased conversion of cholesterol to bile salts as well as disruption of enterohepatic recirculation of bile salts. Support: The Solae Company and NIHAT000826