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.
Highlights
To investigate the importance of factors influencing the fatty acid composition, lipid and lipoprotein metabolism in the rat, the effect of Sthia fatty acids of chain-length ranging from octyl- to hexadecylthioacetic acid were studied
The decrease in plasma triacylglycerol levels by the hypolipidemic 3thia fatty acidswas accompanied by a corresponding reduction in VLDLtriacylglycerols
Administration of these Sthia fatty acids to rats significantly increased the amount of monoenes and especially oleic acid (18: ln-9) in the very low density lipoprotein (VLDL) and low density lipoprotein (LDL) fractions compared to controls
Summary
Chemicals Isotopes used in this experiment were purchased from New England Nuclear (Boston, MA) except for Abbreviations: VLDL, very low density lipoprotein;LDL, low density lipoprotein; HDL, high density lipoprotein. Male Wistar rats weighing between 250-270 g were purchased from Mallegaard Breeding Laboratory, (Ejby,Denmark). They were housed in metal wire cages and maintained on a 12-hlight/dark cycle, at a temperature of 20 t 3°C. The rats were acclimatized for 1week before the start of the experiment and had free access to water and R34EWOSALABgrower rat maintenance chow (Ewos, Sweden) which contained the following fatty acids (mol%); 16:0'(21%),16:ln-7 (2%), 18:O (4%), 18:ln-9 (25%), 18:2n-6 (42%),and 18:3n-3 (6%). Two groups, C13-S and C14Sacetic acid, received a dose of 300 mg/kg body weight per day. Effects of 3-thia fatty acids with different chain-length and palmitic acid (control) on very low density lipoprotein (VLDL) fatty acid composition (mol % of total lipid) after 7 days of treatment
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