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

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 12 alpha-hydroxylated (12 alpha OH) BAs. Although the liver is the metabolic center in our body, the association between hepatic steatosis and 12 alpha OH BAs in HF-fed rats is undear. Thus, we investigated extensively BA composition in HF-fed rats and evaluated the association between hepatic steatosis and 12 alpha OH 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 12 alpha OH BAs concentrations but not with non-12 alpha OH BAs in the feces, portal plasma and liver. Accompanied by the increase in 12 alpha OH BAs, the rats fed HF diet showed increased fat absorption and higher mRNA expression of liver Cidea. The enhancement of 12 alpha OH BA secretion may contribute to hepatic steatosis by the promotion of dietary fat absorption and hepatic Cidea mRNA expression. The increase in 12 alpha OH BAs was associated with enhanced liver cholesterol 7 alpha-hydroxylase (Cyp7a1) and sterol 12 alpha-hydroxylase (Cyp8b1) mRNA expression. There was a significant increase in 7 alpha-hydroxycholesterol, a precursor of BAs, in the liver of HF-fed rats. Altogether, these data suggest that the HF diet increases preferentially 12 alpha OH BAs synthesis by utilizing the accumulated hepatic cholesterol and enhancing mRNA expression of Cyp7a1 and Cyp8b1 in the liver. (C) 2020 Elsevier Inc. All rights reserved.