title: Up-regulated delta 9-desaturase gene expression by hypolipidemic peroxisome-proliferating fatty acids results in increased oleic acid content in liver and VLDL: accumulation of a delta 9-desaturated metabolite of tetradecylthioacetic acid.
abstract: In the liver of rats, monocarboxylic 3-thia fatty acids, tridecylthioacetic acid (C13-S-acetic acid) and tetradecylthioacetic acid (C14-S-acetic acid), increase the mRNA levels of delta 9-desaturase both in a time- and dose-dependent manner. The increased delta 9-desaturase mRNA levels were accompanied by increased delta 9-desaturase activity and increased amounts of oleic acid (18:1 n-9) and delta 9-desaturated C14-S-acetic acid. delta 9-Desaturated C14-S-acetic acid was only detected in phospholipid and cholesterolester species after C14-S-acetic acid treatment. In contrast, C14-S-acetic acid was detected in all the different hepatic lipid fractions, but mainly in the phospholipids. Moreover, C13-S-acetic acid and C14-S-acetic acid were detected in both liver and very low density lipoprotein (VLDL). No delta 9-desaturated 3-thia fatty acid products, however, were found in VLDL. Administration of mono- and dicarboxylic 3-thia fatty acids to rats induced liver expression of the fatty acyl-CoA oxidase gene. After 1 week of C14-S-acetic acid treatment, the levels of fatty acyl-CoA oxidase mRNA increased 5-fold, whereas the delta 9-desaturase mRNA was increased about 1.8-fold. Both fatty acyl-CoA oxidase and delta 9-desaturase mRNA increased about 8-fold after 12 weeks of treatment with C14-S-acetic acid. In conclusion, this study demonstrates that C14-S-acetic acid increases rat delta 9-desaturase gene expression and activity and that changes in hepatic lipids, e.g., 18:1 n-9, are reflected in the VLDL. The peroxisome-proliferating monocarboxylic thia fatty acids are good substrates for desaturases, as delta 9-desaturated metabolites of monocarboxylated thia acids were formed in the liver. Modification of delta 9-desaturation, however, appears not to be related to peroxisome proliferation.
authors.affiliation: Department of Clinical Biology, University of Bergen, Haukeland Hospital, Norway.
authors.forename: L
authors.initials: L
authors.lastname: Madsen
authors.forename: L
authors.initials: L
authors.lastname: Frøyland
authors.forename: H J
authors.initials: HJ
authors.lastname: Grav
authors.forename: R K
authors.initials: RK
authors.lastname: Berge
mesh_terms: D042962:Acyl-CoA Oxidase; D000818:Animals; D002849:Chromatography, Gas; D004587:Electrophoresis, Agar Gel; D005227:Fatty Acids / Q000378:metabolism / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D008830:Microbodies / Q000187:drug effects; D009693:Nucleic Acid Hybridization; D019301:Oleic Acid / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism; D019308:Palmitic Acid / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013230:Stearoyl-CoA Desaturase / Q000235:genetics* / Q000378:metabolism; D013440:Sulfides / Q000378:metabolism* / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D005227:Fatty Acids; D008079:Lipoproteins, VLDL; D012333:RNA, Messenger; D013440:Sulfides; D019301:Oleic Acid; D019308:Palmitic Acid; C062078:1-(carboxymethylthio)tetradecane; D010088:Oxidoreductases; D013230:Stearoyl-CoA Desaturase; D042962:Acyl-CoA Oxidase