Exp Mol Med.  2014 Dec;46(12):e127. 10.1038/emm.2014.90.

Omega-3 polyunsaturated fatty acid and ursodeoxycholic acid have an additive effect in attenuating diet-induced nonalcoholic steatohepatitis in mice

• Kim JK
• Lee KS
• Lee DK
• Lee SY
• Chang HY
• Choi J
• Lee JI

• KMID: 2155392
• DOI: http://doi.org/10.1038/emm.2014.90

Abstract

Nonalcoholic steatohepatitis (NASH) can progress into liver cirrhosis; however, no definite treatment is available. Omega-3 polyunsaturated fatty acid (omega-3) has been reported to alleviate experimental NASH, although its beneficial effect was not evident when tested clinically. Thus, this study aimed to investigate the additive effect of omega-3 and ursodeoxycholic acid (UDCA) on diet-induced NASH in mice. C57BL/6 mice were given a high-fat diet (HFD) for 24 weeks, at which point the mice were divided into three groups and fed HFD alone, HFD with omega-3 or HFD with omega-3 in combination with UDCA for another 24 weeks. Feeding mice an HFD and administering omega-3 improved histologically assessed liver fibrosis, and UDCA in combination with omega-3 further attenuated this disease. The assessment of collagen alpha1(I) expression agreed with the histological evaluation. Omega-3 in combination with UDCA resulted in a significant attenuation of inflammation whereas administering omega-3 alone failed to improve histologically assessed liver inflammation. Quantitative analysis of tumor necrosis factor alpha showed an additive effect of omega-3 and UDCA on liver inflammation. HFD-induced hepatic triglyceride accumulation was attenuated by omega-3 and adding UDCA accentuated this effect. In accordance with this result, the expression of sterol regulatory binding protein-1c decreased after omega-3 administration and adding UDCA further diminished SREBP-1c expression. The expression of inducible nitric oxide synthase (iNOS), which may reflect oxidative stress-induced tissue damage, was suppressed by omega-3 administration and adding UDCA further attenuated iNOS expression. These results demonstrated an additive effect of omega-3 and UDCA for alleviating fibrosis, inflammation and steatosis in diet-induced NASH.

MeSH Terms

Animals
Cholagogues and Choleretics/pharmacology/*therapeutic use
Diet, High-Fat/adverse effects
Drug Synergism
Fatty Acids, Omega-3/pharmacology/*therapeutic use
Fibrosis/drug therapy/etiology/immunology/pathology
Inflammation/drug therapy/etiology/immunology/pathology
Liver/*drug effects/immunology/pathology
Male
Mice, Inbred C57BL
Non-alcoholic Fatty Liver Disease/*drug therapy/etiology/immunology/pathology
Ursodeoxycholic Acid/pharmacology/*therapeutic use
Cholagogues and Choleretics
Fatty Acids, Omega-3
Ursodeoxycholic Acid