The absorption, distribution and biological effects of a modified fatty acid in its free form and as an ethyl ester in rats

Chem Biol Interact. 2009 May 15;179(2-3):227-32. doi: 10.1016/j.cbi.2008.10.004. Epub 2008 Oct 15.

Abstract

It has been demonstrated that the absorption of EPA and DHA is significantly lower for ethyl esters than for the corresponding free fatty acids. Since these fatty acids exist in nature and are catabolized by beta-oxidation, we instead wanted to investigate the absorption, distribution and biological effects of a non-beta-oxidizable modified fatty acid. The modified fatty acid tetradecylthioacetic acid (TTA) and the ethyl ester of TTA (EtTTA) were administered to rats for 10 days, in doses corresponding to 150 mg TTA/kg BW/day. No significant differences were found between the accumulated amounts of TTA or its Delta9 desaturated metabolite in plasma, liver, heart and epididymal white adipose tissue between EtTTA and TTA treated rats. EtTTA and TTA increased the activities of carnitine palmitoyltransferase-II and fatty acyl-CoA oxidase in liver, with no differences between the two treatment groups, but did not affect these activities in heart. EtTTA and TTA treatment decreased the plasma levels of triacylglycerols, cholesterol and phospholipids to similar extents, but no significant effects were seen in hepatic and cardiac lipid levels. EtTTA and TTA had similar effects on the fatty acid composition in plasma, liver, heart and epididymal white adipose tissue. Based on changes in fatty acid indexes it seems that these drugs had comparable stimulating effects on stearoyl-CoA desaturase and Delta6 desaturase, and reduced the Delta5 desaturase activity in liver. From the presented results we conclude that the absorption and distribution of the ethyl ester and the free form of TTA are not significantly different, and that the two administered forms of TTA have similar effects on lipid metabolism in rats.

MeSH terms

  • Acyl-CoA Oxidase / metabolism
  • Animals
  • Carnitine O-Palmitoyltransferase / metabolism
  • Cholesterol / blood
  • Esters / metabolism*
  • Esters / pharmacokinetics*
  • Liver / enzymology
  • Male
  • Phospholipids / blood
  • Rats
  • Rats, Wistar
  • Sulfides / metabolism*
  • Sulfides / pharmacokinetics*
  • Tissue Distribution
  • Triglycerides / blood

Substances

  • Esters
  • Phospholipids
  • Sulfides
  • Triglycerides
  • 1-(carboxymethylthio)tetradecane
  • Cholesterol
  • Acyl-CoA Oxidase
  • Carnitine O-Palmitoyltransferase