Potential for dietary ω-3 fatty acids to prevent nonalcoholic fatty liver disease and reduce the risk of primary liver cancer

Adv Nutr. 2015 Nov 13;6(6):694-702. doi: 10.3945/an.115.009423. Print 2015 Nov.


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, that is, hepatosteatosis. NAFLD ranges in severity from benign fatty liver to nonalcoholic steatohepatitis (NASH), and 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 by using mice with the LDL cholesterol receptor gene ablated 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. With the use of transcriptomic, lipidomic, and metabolomic approaches, we examined the capacity of 2 dietary ω-3 (n-3) 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 at reversing WD effects on hepatic metabolism, oxidative stress, and fibrosis. The outcome of these studies suggests that DHA may be useful in preventing NASH and reducing the risk of HCC.

Keywords: fatty liver disease; fibrosis; inflammation; liver cancer; metabolomics; oxidative stress; ω-3 PUFAs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Diet, Western / adverse effects
  • Dietary Fats, Unsaturated / administration & dosage
  • Dietary Fats, Unsaturated / therapeutic use*
  • Disease Models, Animal
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid
  • Fatty Acids, Omega-3 / administration & dosage
  • Fatty Acids, Omega-3 / therapeutic use*
  • Fatty Liver
  • Hepatitis
  • Humans
  • Liver Cirrhosis
  • Liver Neoplasms / prevention & control*
  • Mice
  • Mice, Knockout
  • Mice, Obese
  • Non-alcoholic Fatty Liver Disease / etiology
  • Non-alcoholic Fatty Liver Disease / prevention & control*
  • Obesity / complications
  • Obesity / epidemiology
  • Obesity / etiology
  • Oxidative Stress
  • Receptors, LDL / deficiency
  • Receptors, LDL / genetics
  • Risk Factors


  • Dietary Fats, Unsaturated
  • Fatty Acids, Omega-3
  • Receptors, LDL
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid