Fish oil alleviates circadian bile composition dysregulation in male mice with NAFLD

May 6, 2019The Journal of nutritional biochemistry

Fish oil improves daily bile balance in male mice with fatty liver disease

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Abstract

Feeding a high-fat diet (HFD) for 12 weeks induced non-alcoholic fatty liver disease (NAFLD) in mice, which was ameliorated by fish oil supplementation.

Bile content was significantly higher at zeitgeber time 0 (ZT0) compared to zeitgeber time 12 (ZT12) across all groups.
Differences in bile composition at ZT0 were associated with amino acid metabolism, fatty acid biosynthesis, and primary bile acid synthesis.
Fish oil supplementation may modify bile composition and influence liver metabolism due to its ω-3 polyunsaturated fatty acids.
ω-3 polyunsaturated fatty acids may also have a role in regulating the circadian rhythm of bile metabolism.

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Our previous studies have found that fish oil rich in ω-3 polyunsaturated fatty acids (ω-3 PUFA) protects against non-alcoholic fatty liver disease (NAFLD) in mice. This study was aimed to explore the effects of fish oil on high fat diet (HFD)-induced circadian bile composition chaos. Male C57BL/6 mice were randomly divided into three groups, a control group (CON), a HFD group and a fish oil (FO) group, which were fed a normal chow diet, a HFD, and a HFD supplemented with FO, respectively for 12 weeks. At the end of the experiment, liver tissue, blood and bile samples were processed at 12-h intervals with the first one at zeitgeber time 0 (ZT0) and the second at zeitgeber time 12 (ZT12). Metabolites in bile were determined using UPLC-QTOF-MS, screened using multivariate statistical analysis, and analyzed using KEGG database and Metaboanalyst. The expression levels of key proteins in bile acid metabolism were examined using western blot. Results of biochemical analysis and H&E staining illustrated that feeding of HFD induced NAFLD, which was ameliorated in FO group. The bile content of each group at ZT0 (CON, HFD, or FO group) was respectively higher than that at ZT12 (P<.05). The metabolic pathway analysis of differential metabolites showed that these differences were correlated with amino acid metabolism, fatty acid biosynthesis and primary bile acid synthesis at ZT0. FO supplement could modify bile composition, which was related to the influence of its ω-3 PUFA on liver metabolism. ω-3 PUFA may also regulate the circadian rhythm of bile metabolism.

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Fish oil alleviates circadian bile composition dysregulation in male mice with NAFLD

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