Degradation of very long chain dicarboxylic polyunsaturated fatty acids in mouse hepatocytes, a peroxisomal process

Biochim Biophys Acta. 2008 Aug;1781(8):400-5. doi: 10.1016/j.bbalip.2008.06.004. Epub 2008 Jun 19.


Polyunsaturated fatty acids can be omega-oxidized to dicarboxylic polyunsaturated fatty acids (DC-PUFA), bioactive compounds which cause vasodilatation and activation of PPARalpha and gamma. DC-PUFA can be shortened by beta-oxidation, and to determine whether mitochondria and/or peroxisomes are responsible for this degradation 20-carboxy-[1-(14)C]-eicosatetraenoic acid (20-COOH-AA) was synthesized and given to hepatocytes from mouse models with peroxisomal dysfunctions. In contrast to wild type cells, hepatocytes from mice with liver-selective elimination of peroxisomes, due to Pex5p deficiency, failed to produce (14)CO(2) and labeled acid-soluble oxidation products, indicating that peroxisomes are involved in the degradation of 20-COOH-AA. Subsequently, the oxidation of 20-COOH-AA was analyzed in hepatocytes lacking multifunctional protein 1 (MFP1) or MFP2, key enzymes of the peroxisomal beta-oxidation. Degradation of 20-COOH-AA was partially impaired in MFP1, but not in MFP2 knockout hepatocytes. Taken together, peroxisomes and not mitochondria are the site of beta-oxidation of DC-PUFA, and MFP1 is involved in this process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Fatty Acids, Unsaturated / analysis
  • Fatty Acids, Unsaturated / biosynthesis
  • Fatty Acids, Unsaturated / metabolism*
  • Hepatocytes / metabolism*
  • Mice
  • Mice, Knockout
  • Oxidation-Reduction
  • Peroxisome-Targeting Signal 1 Receptor
  • Peroxisomes / metabolism*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Time Factors


  • Fatty Acids, Unsaturated
  • Peroxisome-Targeting Signal 1 Receptor
  • Receptors, Cytoplasmic and Nuclear