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

Enterohepatic circulation of 12 alpha-hydroxylated (12 alpha OH) 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 center dot 5 g/kg diet) for 4 weeks. Dietary Raf normalised hepatic TAG levels (two-way ANOVA P < 0 center dot 001 for CA, P = 0 center dot 02 for Raf and P = 0 center dot 004 for interaction) in the CA-supplemented diet-fed rats. Dietary Raf supplementation reduced hepatic 12 alpha OH BA concentration (two-way ANOVA P < 0 center dot 001 for CA, P = 0 center dot 003 for Raf and P = 0 center dot 03 for interaction). The concentration of 12 alpha OH BA was reduced in the aortic and portal plasma. Raf supplementation increased acetic acid concentration in the caecal contents (two-way ANOVA P = 0 center dot 001 as a main effect). Multiple regression analysis revealed that concentrations of aortic 12 alpha OH BA and caecal acetic acid could serve as predictors of hepatic TAG concentration (R (2) = 0 center dot 55, P < 0 center dot 001). However, Raf did not decrease the secondary 12 alpha OH 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 12 alpha OH BA circulation.

Automated summary

The enterohepatic circulation of 12 alpha-hydroxylated bile acid is enhanced in rats fed a high-fat diet, and dietary supplementation of raffinose can normalize hepatic lipid accumulation by suppressing this circulation.