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

 Ja Kyung Kim  ;  Kwan Sik Lee  ;  Dong Ki Lee  ;  Su Yeon Lee  ;  Hye Young Chang  ;  Junjeong Choi  ;  Jung Il Lee 
Journal Title
Issue Date
Animals ; Cholagogues and Choleretics/pharmacology ; Cholagogues and Choleretics/therapeutic use* ; Diet, High-Fat/adverse effects ; Drug Synergism ; Fatty Acids, Omega-3/pharmacology ; Fatty Acids, Omega-3/therapeutic use* ; Fibrosis/drug therapy ; Fibrosis/etiology ; Fibrosis/immunology ; Fibrosis/pathology ; Inflammation/drug therapy ; Inflammation/etiology ; Inflammation/immunology ; Inflammation/pathology ; Liver/drug effects* ; Liver/immunology ; Liver/pathology ; Male ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/drug therapy* ; Non-alcoholic Fatty Liver Disease/etiology ; Non-alcoholic Fatty Liver Disease/immunology ; Non-alcoholic Fatty Liver Disease/pathology ; Ursodeoxycholic Acid/pharmacology ; Ursodeoxycholic Acid/therapeutic use*
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.
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1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Ja Kyung(김자경) ORCID logo https://orcid.org/0000-0001-5025-6846
Lee, Kwan Sik(이관식) ORCID logo https://orcid.org/0000-0002-3672-1198
Lee, Dong Ki(이동기) ORCID logo https://orcid.org/0000-0002-0048-9112
Lee, Su Yeon(이수연)
Lee, Jung Il(이정일) ORCID logo https://orcid.org/0000-0002-0142-1398
Chang, Hye Young(장혜영)
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