Association between 12α-hydroxylated bile acids and hepatic steatosis in rats fed a high-fat diet

Jun 14, 2020The Journal of nutritional biochemistry

Link between specific bile acids and liver fat buildup in rats on a high-fat diet

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Abstract

High-fat diet feeding increased hepatic triglyceride and total cholesterol concentrations in rats.

Hepatic triglyceride and cholesterol levels positively correlated with 12α-hydroxylated bile acid concentrations.
Rats on a high-fat diet showed increased fat absorption and higher liver mRNA expression of Cidea.
The increase in 12α-hydroxylated bile acids may contribute to hepatic steatosis.
Enhanced liver mRNA expression of cholesterol 7α-hydroxylase and sterol 12α-hydroxylase was observed.
A significant rise in 7α-hydroxycholesterol, a bile acid precursor, was noted in the livers of high-fat diet-fed rats.

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High-fat (HF) diet induces hepatic steatosis that is a risk factor for noncommunicable diseases such as obesity, type 2 diabetes and cardiovascular disease. Previously, we found that HF feeding in rats increases the excretion of fecal bile acids (BAs), specifically 12α-hydroxylated (12αOH) BAs. Although the liver is the metabolic center in our body, the association between hepatic steatosis and 12αOH BAs in HF-fed rats is unclear. Thus, we investigated extensively BA composition in HF-fed rats and evaluated the association between hepatic steatosis and 12αOH BAs. Acclimated male inbred WKAH/HkmSlc rats were divided into two groups and fed either control or HF diet for 8 weeks. Feeding HF diet increased hepatic triglyceride and total cholesterol concentrations, which correlated positively with 12αOH BAs concentrations but not with non-12αOH BAs in the feces, portal plasma and liver. Accompanied by the increase in 12αOH BAs, the rats fed HF diet showed increased fat absorption and higher mRNA expression of liver Cidea. The enhancement of 12αOH BA secretion may contribute to hepatic steatosis by the promotion of dietary fat absorption and hepatic Cidea mRNA expression. The increase in 12αOH BAs was associated with enhanced liver cholesterol 7α-hydroxylase (Cyp7a1) and sterol 12α-hydroxylase (Cyp8b1) mRNA expression. There was a significant increase in 7α-hydroxycholesterol, a precursor of BAs, in the liver of HF-fed rats. Altogether, these data suggest that the HF diet increases preferentially 12αOH BAs synthesis by utilizing the accumulated hepatic cholesterol and enhancing mRNA expression of Cyp7a1 and Cyp8b1 in the liver.

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Association between 12α-hydroxylated bile acids and hepatic steatosis in rats fed a high-fat diet

Abstract

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