Eicosapentaenoic acid inhibits formation of cholesterol gallstone by suppressing gene HMGCR and ABCG5/8 in mice

Abstract

Objective To observe the effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on cholesterol gallstones formation in C57BL/6 mice with diet-induced cholesterol gallstone, and then explore the potential mechanism. Methods Fifty C57BL/6 mice were randomly divided into 5 groups (10 mice in each group), referring to control group, experimental group, experimental plus DHA group, experimental plus EPA group, as well as experimental plus DHA and EPA group. The mice in control group were fed with regular diet, and the rest of the mice with lithogenic diet (LD). Subsequent to feeding the mice with separate diets for two weeks, EPA and/or DHA (70 mg·kg-1·d-1) were orally administered for eight weeks, while the LD feeding was continued during this period. After a total of 10 weeks, the mice were dissected to observe the gallstone formation. The levels of serum lipids, total cholesterol (TC) and phospholipids (PL) in bile, and TC in the liver were tested, and the protein expression of HMGCR, SRBI, ABCG5/ABCG8, CYP7A1 and ABCB11genes in the liver of mice was measured. Results Compared with the experimental group, the experimental plus EPA group had significantly lower TC in liver (0.033±0.008 mmolo/g) and bile (1.807±0.381 mmolo/L), and lower relative protein expression levels of HMGCR (0.545±0.098), ABCG5 (0.418±0.089) and ABCG8 (0.501±0.151)in liver (P 0.05). Conclusions EPA could prevent the cholesterol gallstone formation in mice by decreasing the expression of HMGCR and ABCG5/8 genes in liver, therefore reducing cholesterol synthesis and blocking cholesterol transport from liver to bile as well as diminishing cholesterol content in the bile. However, the inhibition effect of DHA on cholesterol gallstone formation was not obvious. Key words: Eicosapentaenoic acid; Mice; Cholesterol gallstone; Gene