Deleterious effect of n-3 polyunsaturated fatty acids in non-alcoholic steatohepatitis in the fat-1 mouse model

Diana Shefer-Weinberg, Shlomo Sasson, Betty Schwartz, Nurit Argov-Argaman, Oren Tirosh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of pathologies, ranging from hepatocellular steatosis to non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. It has been suggested that fish oil containing n-3 polyunsaturated fatty acids (n-3 PUFA) induce beneficial effects in NAFLD. However, n-3 PUFA are sensitive to peroxidation that generate free radicals and reactive aldehydes. We aimed at determining whether changing the tissue ratio of n-3 to n-6 PUFA may be beneficial or alternatively harmful to the etiology of NAFLD. The transgenic Fat-1 mouse model was used to determine whether n-3 PUFA positively or negatively affect the development of NAFLD. fat-1mice express the fat-1 gene of Caenorhabditis elegans, which encodes an n-3 fatty-acid desaturase that converts n-6 to n-3 fatty acids. Wild-type C57BL/6 mice served as the control group. Both groups of mice were fed methionine and choline deficient (MCD) diet, which induces NASH within 4 weeks. The study shows that NASH developed faster and was more severe in mice from the fat-1 group when compared to control C57BL/6 mice. This was due to enhanced lipid peroxidation of PUFA in the liver of the fat-1 mice as compared to the control group. Results of our mice study suggest that supplementing the diet of individuals who develop or have fatty livers with n-3 PUFA should be carefully considered and if recommended adequate antioxidants should be added to the diet in order to reduce such risk.

Original languageAmerican English
Pages (from-to)37-49
Number of pages13
JournalClinical Nutrition Experimental
StatePublished - 1 Apr 2017

Bibliographical note

Publisher Copyright:
© 2016


  • Fat-1
  • Fatty liver
  • Lipids
  • Oxidative stress
  • n-3 PUFA


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