title: Degradation of very long chain dicarboxylic polyunsaturated fatty acids in mouse hepatocytes, a peroxisomal process.
abstract: 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.
authors.affiliation: Laboratory of Lipid Biochemistry and Protein Interactions, Department of Molecular Cell Biology, KU Leuven, Leuven, Belgium.
authors.forename: Su Duy
authors.initials: SD
authors.lastname: Nguyen
authors.forename: Myriam
authors.initials: M
authors.lastname: Baes
authors.forename: Paul P
authors.initials: PP
authors.lastname: Van Veldhoven
mesh_terms: D000818:Animals; D005231:Fatty Acids, Unsaturated / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D000074435:Peroxisome-Targeting Signal 1 Receptor; D020675:Peroxisomes / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D013997:Time Factors
chemical_list: D005231:Fatty Acids, Unsaturated; D000074435:Peroxisome-Targeting Signal 1 Receptor; D018160:Receptors, Cytoplasmic and Nuclear