Dietary raffinose ameliorates hepatic lipid accumulation induced by cholic acid via modulation of enterohepatic bile acid circulation in rats.

Enterohepatic circulation of 12-hydroxylated (12OH) bile acid (BA) is enhanced depending on the energy intake in high-fat diet-fed rats. Such BA metabolism can be reproduced using a diet supplemented with cholic acid (CA), which also induces simple steatosis, without inflammation and fibrosis, accompanied by some other symptoms that are frequently observed in the condition of non-alcoholic fatty liver in rats. We investigated whether supplementation of the diet with raffinose (Raf) improves hepatic lipid accumulation induced by the CA-fed condition in rats. After acclimation to the AIN-93-based control diet, male Wistar rats were fed diets supplemented with a combination of Raf (30 g/kg diet) and/or CA (0·5 g/kg diet) for 4 weeks. Dietary Raf normalised hepatic TAG levels (two-way ANOVA < 0·001 for CA, = 0·02 for Raf and = 0·004 for interaction) in the CA-supplemented diet-fed rats. Dietary Raf supplementation reduced hepatic 12OH BA concentration (two-way ANOVA < 0·001 for CA, = 0·003 for Raf and = 0·03 for interaction). The concentration of 12OH BA was reduced in the aortic and portal plasma. Raf supplementation increased acetic acid concentration in the caecal contents (two-way ANOVA = 0·001 as a main effect). Multiple regression analysis revealed that concentrations of aortic 12OH BA and caecal acetic acid could serve as predictors of hepatic TAG concentration ( = 0·55, < 0·001). However, Raf did not decrease the secondary 12OH BA concentration in the caecal contents as well as the transaminase activity in the CA diet-fed rats. These results imply that dietary Raf normalises hepatic lipid accumulation via suppression of enterohepatic 12OH BA circulation.