The ratio of 12α to non-12-hydroxylated bile acids reflects hepatic triacylglycerol accumulation in high-fat diet-fed C57BL/6J mice

Abstract

In our previous study, enterohepatic 12α-hydroxylated (12α) bile acid (BA) levels were found to be correlated with hepatic triacylglycerol concentration in rats fed high-fat (HF) diet. Since BA composition is diverse depending on animal species, we evaluated whether such a relationship is applicable in mice in response to an HF diet. C57BL/6JJmsSLC (B6) male mice were fed HF diet for 13 weeks and analyzed for triacylglycerol, cholesterol, oxysterols, and other metabolites in the liver. The BA composition was determined in the liver, small intestinal contents, portal plasma, aortic plasma, and feces. Neutral sterols were also measured in the feces. The ratio of 12α BA/non-12 BA increased in the liver, portal plasma, small intestinal contents, and feces of HF-fed B6 mice. Moreover, a positive correlation was observed between the ratio of fecal 12α BAs/non-12 BAs and hepatic triacylglycerol concentration. The concentration of 7α-hydroxycholesterol was increased in the liver of HF-fed B6 mice, whereas no increase was observed in the hepatic expression of cytochrome P450 family 7 subfamily A member 1. The present study showed that the ratio of 12α BA/non-12 BA in feces is closely associated with hepatic triacylglycerol accumulation in B6 mice fed HF diet.

Impact of high fat diet and exercise on bone and bile acid metabolism in rats

“…This observation, which is supported by a previous study in rats (29), alludes to a preferential use of TCA in lipid absorption and a better intestinal reabsorption than CA. In stool, the 12-α-hydroxylated / non 12-α-hydroxylated ratio, which has been found to be correlated with type II diabetes (61) and liver fat content (65), was 5-fold higher upon HFD treatment. Another striking result was the marked elevation of the DCA/CA ratio in HFD animals, which suggests that dietary fat intake modulates bacterial 7α-dehydroxylation in the gut.…”

Impact of High-Fat Diet and Exercise on Bone and Bile Acid Metabolism in Rats

“…This observation, which is supported by a previous study in rats [ 29 ], alludes to a preferential use of TCA in lipid absorption and a better intestinal reabsorption than CA. In stool, the 12-α-hydroxylated/non-12-α-hydroxylated ratio, which has been found to be correlated with type 2 diabetes [ 61 ] and liver fat content [ 65 ], was 5-fold higher upon HFD treatment. Another striking result was the marked elevation of the DCA/CA ratio in HFD animals, which suggests that dietary fat intake modulates bacterial 7α-dehydroxylation in the gut.…”