Omega-3 polyunsaturated fatty acid and ursodeoxycholic acid have an additive effect in attenuating diet-induced nonalcoholic steatohepatitis in mice.
- Author:
Ja Kyung KIM
1
;
Kwan Sik LEE
;
Dong Ki LEE
;
Su Yeon LEE
;
Hye Young CHANG
;
Junjeong CHOI
;
Jung Il LEE
Author Information
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- MeSH: 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
- From:Experimental & Molecular Medicine 2014;46(12):e127-
- CountryRepublic of Korea
- Language:English
- 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.
