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

Abstract

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 eight 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 7αhydroxylase (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.

Flaxseed Powder Attenuates Non-Alcoholic Steatohepatitis via Modulation of Gut Microbiota and Bile Acid Metabolism through Gut–Liver Axis

“…Recently, a study suggested the 12αOH-to-non-12αOH BA ratio was extremely high in NASH patients [ 54 ]. The increased secretion of 12αOH BA may lead to hepatic steatosis by promoting fat absorption and liver Cidea mRNA expression [ 16 ]. The increase in 12αOH BAs had an association with enhancements of liver Cyp7a1 and Cyp8b1 mRNA expression.…”

“…An increase in 12α-OH BA levels in NASH patients has been identified [ 6 ]. Recent studies have also revealed that higher plasma 12αOH/non-12αOH BA ratios were related to lower insulin sensitivity in humans [ 15 ] and that fecal 12αOH Bas were strongly associated with hepatic steatosis [ 16 ]. Therefore, regulating BA metabolism might be an effective strategy to prevent NAFLD and related disorders [ 17 ].…”

High-Fat Diets-Induced Metabolic Disorders to Study Molecular Mechanism of Hyperlipidemia in Rats

“…One of the causes of lipid metabolism disorders is increased Free Fatty Acids (FFAs) in the blood (24,28,35). Figure 2.…”

“…This stimulated the migration of M1 macrophages. M1 macrophages infiltrate adipose tissue and secrete many pro-inflammatory cytokines, including IL-6, IL-12, and tumor necrosis factor-α (TNF-α) (2,35,49). In addition to increasing the activity of M1 macrophages, HFD also decreases the activity of regulatory T cells and macrophages M2, both of which are anti-inflammatory cells (9).…”

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

“…In rat experiments, excessive energy consumption in the form of a high-fat diet enhances the secretion of 12α-hydroxylated (12αOH) bile acid (BA) (6) . In addition, 12αOH BA concentrations in the liver, portal blood, and faeces are associated with hepatic lipid accumulation (7) . Such an association has also been reported between 12αOH BAs and fatty liver index in a clinical study (8) .…”