Effect of 3-thia fatty acids on the lipid composition of rat liver, lipoproteins, and heart.
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.
Frøyland
L
L
Department of Clinical Biology, University of Bergen, Haukeland Hospital, Norway.
Madsen
L
L
Sjursen
W
W
Garras
A
A
Lie
O
O
Songstad
J
J
Rustan
A C
AC
Berge
R K
RK
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
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