Fish oil fed prior to ethanol administration prevents acute ethanol-induced fatty liver in mice

J Hepatol. 2008 Sep;49(3):441-50. doi: 10.1016/j.jhep.2008.04.026. Epub 2008 Jun 11.

Abstract

Background/aims: We examined whether dietary fish oil can prevent acute ethanol (alcohol)-induced fatty liver.

Methods: Mice were fed safflower oil, fish oil, or safflower oil plus a PPAR alpha activator on the day prior to ethanol administration. Oil red O staining, serum analysis, and RT-PCR were used to analyze ethanol-induced fatty liver.

Results: In mice fed safflower oil, ethanol increased liver TG 3-fold, with activation of SREBP-1c and ChREBP, which promote de novo lipogenesis, and increases in expression of mRNAs for PPAR gamma and DGATs mRNAs, which promote TG synthesis. When mice were fed fish oil, ethanol-induced fatty liver was reduced by 73%. Fish oil decreased SREBP-1c activity and increased PPAR alpha activity. However, levels of DGAT1, DGAT2, ChREBP, LPK, and PPAR gamma mRNAs were increased in response to ethanol in mice fed fish oil. Prior administration of Wy14643, PPAR alpha activator, did not inhibit ethanol-induced fatty liver, suggesting that PPAR alpha played little role in prevention of ethanol-induced fatty liver by fish oil.

Conclusions: A single dose of ethanol increases the liver TG level via several mechanisms; however, prior ingestion of fish oil effectively prevents ethanol-induced fatty liver, at least in part, by decreasing basal SREBP-1c activity, especially a marked reduction in SCD1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticholesteremic Agents / pharmacology
  • Blood Glucose / metabolism
  • Dietary Fats, Unsaturated / administration & dosage
  • Dietary Fats, Unsaturated / pharmacology
  • Dietary Fats, Unsaturated / therapeutic use*
  • Dose-Response Relationship, Drug
  • Ethanol / adverse effects*
  • Fatty Acids, Nonesterified / blood
  • Fatty Liver / chemically induced*
  • Fatty Liver / metabolism
  • Fatty Liver / prevention & control*
  • Fish Oils / administration & dosage
  • Fish Oils / pharmacology
  • Fish Oils / therapeutic use*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • PPAR gamma / metabolism
  • Pyrimidines / pharmacology
  • Safflower Oil / therapeutic use
  • Stearoyl-CoA Desaturase / metabolism
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • Triglycerides / metabolism

Substances

  • Anticholesteremic Agents
  • Blood Glucose
  • Dietary Fats, Unsaturated
  • Fatty Acids, Nonesterified
  • Fish Oils
  • PPAR gamma
  • Pyrimidines
  • Srebf1 protein, mouse
  • Sterol Regulatory Element Binding Protein 1
  • Triglycerides
  • Ethanol
  • Safflower Oil
  • pirinixic acid
  • Scd1 protein, mouse
  • Stearoyl-CoA Desaturase