Paper
Hypocholesterolemic Effect of Dietary Apple Polyphenol Is Associated with Alterations in Hepatic Gene Expression Related to Cholesterol Metabolism in Rats
- Authors:
- Tadahiro Sunagawa; Yutaka Ohta; Manabu Sami; Tomomasa Kanda; Kyoichi Osada
- Abstract
- Apple polyphenol (AP) mainly consists of procyanidins and has been reported to improve blood cholesterol levels and promote excretion of cholesterol in rats fed high-cholesterol diets. To understand the molecular mechanisms underlying the effects of AP, we investigated whether dietary AP changed the hepatic expression of genes related to cholesterol metabolism and steroid transport. Four-week-old male Sprague-Dawley rats were pair-fed with diets containing 0.5% cholesterol together with 0% (control), 0.2%, and 0.5% AP, respectively, for 30 days. Administration of 0.5% AP was found to improve serum total cholesterol levels (0.69-fold vs. control, p < 0.05), and increase hepatic LDL receptor (LDLR) mRNA (1.59-fold vs. control, p < 0.0001). There was a negative correlation between serum non-HDL cholesterol and LDLR mRNA (p < 0.001). Administration of 0.5% AP increased excretion of primary bile acids (2.96-fold vs. control, p < 0.0001) and up-regulated the expression of steroid catabolism genes such as sterol 12α-hydroxylase (CYP8B1). However, improvements in cholesterol levels were not associated with the hepatic expression of cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid biosynthesis. Expression of farnesoid X receptor (FXR), which is involved in the regulation of bile acid biosynthesis, was up-regulated by 0.5% AP (1.56-fold vs. control, p < 0.01), and FXR mRNA levels correlated positively with bile acid excretion (p < 0.01). These results show that dietary AP improved blood cholesterol levels with adequate intake of LDL from blood by increasing hepatic LDLR expression and promoting production of bile acid with an up-regulation of genes related to steroid catabolism.
- Keywords
- Apple Polyphenol; Procyanidin; Cholesterol Metabolism; LDL Receptor
- StartPage
- 50
- EndPage
- 58
- Doi
- 10.5963/LSMR0302002