Highly purified eicosapentaenoic acid prevents the progression of hepatic steatosis by repressing monounsaturated fatty acid synthesis in high-fat/high-sucrose diet-fed mice

Prostaglandins Leukot Essent Fatty Acids. 2009 Apr;80(4):229-38. doi: 10.1016/j.plefa.2009.02.004. Epub 2009 Mar 27.


Eicosapentaenoic acid (EPA) is a member of the family of n-3 polyunsaturated fatty acids (PUFAs) that are clinically used to treat hypertriglyceridemia. The triglyceride (TG) lowering effect is likely due to an alteration in lipid metabolism in the liver, but details have not been fully elucidated. To assess the effects of EPA on hepatic TG metabolism, mice were fed a high-fat and high-sucrose diet (HFHSD) for 2 weeks and were given highly purified EPA ethyl ester (EPA-E) daily by gavage. The HFHSD diet increased the hepatic TG content and the composition of monounsaturated fatty acids (MUFAs). EPA significantly suppressed the hepatic TG content that was increased by the HFHSD diet. EPA also altered the composition of fatty acids by lowering the MUFAs C16:1 and C18:1 and increasing n-3 PUFAs, including EPA and docosahexaenoic acid (DHA). Linear regression analysis revealed that hepatic TG content was significantly correlated with the ratios of C16:1/C16:0, C18:1/C18:0, and MUFA/n-3 PUFA, but was not correlated with the n-6/n-3 PUFA ratio. EPA also decreased the hepatic mRNA expression and nuclear protein level of sterol regulatory element binding protein-1c (SREBP-1c). This was reflected in the levels of lipogenic genes, such as acetyl-CoA carboxylase alpha (ACCalpha), fatty acid synthase, stearoyl-CoA desaturase 1 (SCD1), and glycerol-3-phosphate acyltransferase (GPAT), which are regulated by SREBP-1c. In conclusion, oral administration of EPA-E ameliorates hepatic fat accumulation by suppressing TG synthesis enzymes regulated by SREBP-1 and decreases hepatic MUFAs accumulation by SCD1.

MeSH terms

  • Animals
  • Dietary Fats / administration & dosage
  • Dietary Fats / adverse effects
  • Eicosapentaenoic Acid / administration & dosage
  • Eicosapentaenoic Acid / analogs & derivatives*
  • Fatty Acids, Monounsaturated / antagonists & inhibitors*
  • Fatty Acids, Monounsaturated / metabolism
  • Fatty Liver / drug therapy*
  • Fatty Liver / etiology
  • Fatty Liver / metabolism
  • Gene Expression / drug effects
  • Gene Expression / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Stearoyl-CoA Desaturase / metabolism
  • Sterol Regulatory Element Binding Protein 1 / antagonists & inhibitors
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • Sucrose / administration & dosage
  • Sucrose / adverse effects
  • Triglycerides / antagonists & inhibitors
  • Triglycerides / metabolism


  • Dietary Fats
  • Fatty Acids, Monounsaturated
  • Sterol Regulatory Element Binding Protein 1
  • Triglycerides
  • Sucrose
  • eicosapentaenoic acid ethyl ester
  • Eicosapentaenoic Acid
  • Scd1 protein, mouse
  • Stearoyl-CoA Desaturase