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Potential for Dietary ω-3 Fatty Acids to Prevent Nonalcoholic Fatty Liver Disease and Reduce the Risk of Primary Liver Cancer

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https://ir.library.oregonstate.edu/concern/articles/0c483m34b

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Abstract
  • Nonalcoholic fatty liver disease (NAFLD) has increased in parallel with central obesity and its prevalence is anticipated to increase as the obesity epidemic remains unabated. NAFLD is now the most common cause of chronic liver disease in developed countries and is defined as excessive lipid accumulation in the liver, i.e., hepatosteatosis. NAFLD ranges in severity from benign fatty liver to nonalcoholic steatohepatitis (NASH), where NASH is characterized by hepatic injury, inflammation, oxidative stress and fibrosis. NASH can progress to cirrhosis; and cirrhosis is a risk factor for primary hepatocellular carcinoma (HCC). The prevention of NASH will lower the risk of cirrhosis and NASH-associated HCC. Our studies have focused on NASH prevention. We developed a model of NASH using Ldlr[superscript -/-] mice fed the western diet (WD). The WD induces a NASH phenotype in these mice that is similar to that seen in humans; and includes robust induction of hepatic steatosis, inflammation, oxidative stress and fibrosis. Using transcriptomic, lipidomic and metabolomic approaches, we examined the capacity of 2 dietary ω3 polyunsaturated fatty acids, eicosapentaenoic acid (20:5ω-3; EPA) and docosahexaenoic acid (22:6ω-3; DHA), to prevent WD-induced NASH. Dietary DHA was superior to EPA at attenuating WD-induced changes in plasma lipids and hepatic injury; and reversing WD effects on hepatic metabolism, oxidative stress, and fibrosis. The outcome of these studies suggests that DHA may be useful in the prevention of NASH and reducing the risk of HCC.
  • This article is a review from the SPLIT D—Surrogate Markers for Cancer Intervention Trials Session presented at the American Institute for Cancer Research (AICR) Conference on Food, Nutrition, Physical Activity and Cancer held 29–31 October 2014 in Washington, DC.
  • Keywords: inflammation, liver cancer, oxidative stress, metabolomics, fibrosis, ω-3 PUFAs, fatty liver disease
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  • Jump, D. B., Depner, C. M., Tripathy, S., & Lytle, K. A. (2015). Potential for Dietary ω-3 Fatty Acids to Prevent Nonalcoholic Fatty Liver Disease and Reduce the Risk of Primary Liver Cancer. Advances in Nutrition: An International Review Journal, 6(6), 694-702. doi:10.3945/an.115.009423
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  • 6
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  • 6
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  • Washington, DC, USA
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  • Supported by National Institute of Food and Agriculture grant 2009-65200-05846 and NIH grants DK 43220 and DK094600.
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