Beneficial effects of omega-3 fatty acids on the consequences of a fructose diet are not mediated by PPAR delta or PGC1 alpha

Eur J Nutr. 2013 Dec;52(8):1865-74. doi: 10.1007/s00394-012-0488-0. Epub 2012 Dec 27.

Abstract

Purpose: To study, in high-fructose-fed rats, the effect of a dietary enrichment in omega-3 polyunsaturated fatty acids (n-3 PUFA) on the expression of genes involved in lipid metabolism and cardiovascular function.

Methods: Twenty-eight male "Wistar Han" rats received for 8 weeks, either a standard chow food or an isocaloric 67% fructose diet enriched or not in alpha-linolenic acid (ALA) or in docosahexaenoic (DHA) and eicosapentaenoic acids (EPA) mix (DHA/EPA). After sacrifice, blood was withdrawn for biochemical analyses; heart, periepididymal adipose tissue and liver were collected and analyzed for the expression of 22 genes by real-time PCR.

Results: Fructose intake resulted in an increase in liver weight and triglyceride content, plasma triglyceride and cholesterol concentrations, although no difference in glucose and insulin. In the liver, lipogenesis was promoted as illustrated by an increase in stearoyl-CoA desaturase and fatty acid synthase (Fasn) together with a decrease in PPAR gamma, delta and PPAR gamma coactivator 1 alpha (PGC1 alpha) expression. In the heart, Fasn and PPAR delta expression were increased. The addition of ALA or DHA/EPA into the diet resulted in a protection against fructose effects except for the decreased expression of PPARs in the liver that was not counterbalanced by n-3 PUFA suggesting that n-3 PUFA and fructose act independently on the expression of PPARs and PGC1 alpha.

Conclusions: In liver, but not in heart, the fructose-enriched diet induces an early tissue-specific reduction in PPAR gamma and delta expression, which is insensitive to n-3 PUFA intake and dissociated from lipogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Animals
  • Blood Glucose / metabolism
  • Cholesterol / blood
  • Diet
  • Fatty Acid Synthases / metabolism
  • Fatty Acids, Omega-3 / pharmacology*
  • Fructose / administration & dosage*
  • Fructose / adverse effects
  • Gene Expression Regulation
  • Insulin / blood
  • Lipid Metabolism / drug effects
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Organ Size / drug effects
  • PPAR delta / metabolism*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Rats
  • Rats, Wistar
  • Real-Time Polymerase Chain Reaction
  • Receptors, LDL / genetics
  • Receptors, LDL / metabolism
  • Stearoyl-CoA Desaturase / metabolism
  • Transcription Factors / metabolism*
  • Triglycerides / blood

Substances

  • Blood Glucose
  • Fatty Acids, Omega-3
  • Insulin
  • Membrane Transport Proteins
  • PPAR delta
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, rat
  • Receptors, LDL
  • Sorl1 protein, rat
  • Transcription Factors
  • Triglycerides
  • Fructose
  • Cholesterol
  • Stearoyl-CoA Desaturase
  • Fatty Acid Synthases