title: Omega-3 polyunsaturated fatty acid and ursodeoxycholic acid have an additive effect in attenuating diet-induced nonalcoholic steatohepatitis in mice.
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 α1(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 α 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.
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Ja Kyung
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Kwan Sik
authors.initials: KS
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Dong Ki
authors.initials: DK
authors.lastname: Lee
authors.affiliation: Medical Research Center, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Su Yeon
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Medical Research Center, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Chang
authors.affiliation: Department of Pathology, Yonsei University Wonju College of Medicine, Wonju, Korea.
authors.forename: Junjeong
authors.initials: J
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jung Il
authors.initials: JI
authors.lastname: Lee
mesh_terms: D000818:Animals; D002756:Cholagogues and Choleretics / Q000494:pharmacology / Q000627:therapeutic use*; D059305:Diet, High-Fat / Q000009:adverse effects; D004357:Drug Synergism; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology / Q000627:therapeutic use*; D005355:Fibrosis / Q000188:drug therapy / Q000209:etiology / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology / Q000276:immunology / Q000473:pathology; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology / Q000473:pathology; D014580:Ursodeoxycholic Acid / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D002756:Cholagogues and Choleretics; D015525:Fatty Acids, Omega-3; D014580:Ursodeoxycholic Acid