Docosapentaenoic acid (22:5n-3) down-regulates the expression of genes involved in fat synthesis in liver cells

Prostaglandins Leukot Essent Fatty Acids. Sep-Oct 2011;85(3-4):155-61. doi: 10.1016/j.plefa.2011.06.002. Epub 2011 Jul 31.

Abstract

Previous studies have shown that Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) exhibit triacylglycerol (TAG) lowering effect in vitro and in vivo by down-regulating the Sterol Regulating Element Binding Protein (SREBP-1c) and reducing the expression levels of lipogenic genes. However, there is no evidence on the effect of Docosapentaenoic Acid (DPA) on SREBP-1c expression levels. DPA is a long chain n-3 fatty acid present in our diet through fish, red meat and milk of ruminant animals. Therefore, this study aimed to elucidate the effect of DPA on liver fatty acid synthesis in an in vitro model using rat liver cells. Our results suggested that DPA incubation (50μM) for 48h (like EPA and DHA) caused a significant decrease in the mRNA expression levels of SREBP-1c, 3-Hydroxy-3-Methyl-Glutaryl-Coenzyme A reductase (HMG-CoA reductase), Acetyl Coenzyme A Carboxylase (ACC-1) and Fatty Acid Synthase (FASn) compared with Oleic Acid (OA) and also a decrease in the protein levels of SREBP-1 and ACC-1. A time-course fatty acid analysis showed that DPA and EPA are interconvertable in the cells; however, after 8h of incubation with DPA, the cell phospholipids contained mainly DPA. The gene expression profiling of the lipogenic genes repeated at 8h confirmed that the inhibitory effect of DPA on mRNA expression levels of the lipogenic genes was most likely due to DPA itself and not due to its conversion into EPA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyl-CoA Carboxylase / genetics
  • Acetyl-CoA Carboxylase / metabolism
  • Animals
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
  • Cell Line, Tumor
  • Down-Regulation
  • Fatty Acid Synthase, Type I / genetics
  • Fatty Acid Synthase, Type I / metabolism
  • Fatty Acids, Omega-3 / pharmacology
  • Fatty Acids, Unsaturated / pharmacology*
  • Gene Expression Regulation
  • Hepatocytes / drug effects*
  • Hepatocytes / metabolism
  • Hydroxymethylglutaryl CoA Reductases / genetics
  • Hydroxymethylglutaryl CoA Reductases / metabolism
  • Lipogenesis / drug effects
  • Lipogenesis / genetics*
  • Liver / cytology
  • Liver / metabolism*
  • Oleic Acid / pharmacology
  • Rats
  • Sterol Regulatory Element Binding Protein 1 / genetics
  • Sterol Regulatory Element Binding Protein 1 / metabolism

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Fatty Acids, Omega-3
  • Fatty Acids, Unsaturated
  • MLXIPL protein, human
  • Sterol Regulatory Element Binding Protein 1
  • Oleic Acid
  • Hydroxymethylglutaryl CoA Reductases
  • FASN protein, human
  • Fatty Acid Synthase, Type I
  • Acetyl-CoA Carboxylase
  • docosapentaenoic acid