title: Effect of 3-thia fatty acids on the lipid composition of rat liver, lipoproteins, and heart.
abstract: To investigate the importance of factors influencing the fatty acid composition, lipid and lipoprotein metabolism in the rat, the effect of 3-thia fatty acids of chain-length ranging from octyl- to hexadecylthioacetic acid were studied. In liver, very low density lipoprotein (VLDL), and low density lipoprotein (LDL), the hypolipidemic 3-thia fatty acids, namely C12-S-acetic acid to C14-S-acetic acid increased the amount of monoenes, especially oleic acid (18:ln-9). In contrast, the content of polyunsaturated fatty acids in liver, VLDL, and LDL decreased, mostly attributed to a reduction of eicosapentaenoic acid (EPA, 20:5n-3). Noteworthy, the hypolipidemic 3-thia fatty acids reduced the amount of arachidonic acid (AA, 20:4n-6) in LDL and HDL. 3-Thia fatty acids accumulated in the liver. In heart, as in liver, 3-thia fatty acids replaced fatty acids of chain-length homologues. In contrast to liver, we were unable to detect any changes in 18:ln-9. However, the n-3 polyunsaturated fatty acid content increased, particularly 20:5n-3 and docosahexaenoic acid (DHA, 22:6n-3) leading to an increased n-3/n-6 ratio. In conclusion, this study demonstrates that hypolipidemic 3-thia fatty acids change the fatty acid composition of organs and lipoproteins. These changes are linked to the expression and activity of hepatic delta9-desaturase, fatty acid oxidation, and displacement of normal fatty acids by 3-thia fatty acids. The fatty acid composition is regulated differently in liver and heart after administration of hypolipidemic 3-thia fatty acids.
authors.affiliation: Department of Clinical Biology, University of Bergen, Haukeland Hospital, Norway.
authors.forename: L
authors.initials: L
authors.lastname: Frøyland
authors.forename: L
authors.initials: L
authors.lastname: Madsen
authors.forename: W
authors.initials: W
authors.lastname: Sjursen
authors.forename: A
authors.initials: A
authors.lastname: Garras
authors.forename: O
authors.initials: O
authors.lastname: Lie
authors.forename: J
authors.initials: J
authors.lastname: Songstad
authors.forename: A C
authors.initials: AC
authors.lastname: Rustan
authors.forename: R K
authors.initials: RK
authors.lastname: Berge
mesh_terms: D000818:Animals; D044943:Fatty Acid Desaturases / Q000235:genetics; D005227:Fatty Acids / Q000737:chemistry* / Q000494:pharmacology*; D015525:Fatty Acids, Omega-3 / Q000737:chemistry / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry*; D008074:Lipoproteins / Q000737:chemistry / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D044925:Oxidoreductases Acting on CH-CH Group Donors; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012339:RNA, Ribosomal, 28S / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013230:Stearoyl-CoA Desaturase / Q000235:genetics; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000494:pharmacology
chemical_list: D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D008055:Lipids; D008074:Lipoproteins; D012333:RNA, Messenger; D012339:RNA, Ribosomal, 28S; D013438:Sulfhydryl Compounds; D044943:Fatty Acid Desaturases; D013230:Stearoyl-CoA Desaturase; D044925:Oxidoreductases Acting on CH-CH Group Donors; C100153:2,4-dienoyl-CoA reductase