Thia fatty acids with the sulfur atom in even or odd positions have opposite effects on fatty acid catabolism.

As tools for mechanistic studies on lipid metabolism, with the long-term goal of developing a drug for the treatment of lipid disorders, thia FA with the sulfur atom inserted at positions 3-9 from the carboxyl group were fed to male Wistar rats for 1 wk to determine their impact on key parameters in lipid metabolism and hepatic levels of thia FA metabolites. Thia FA with the sulfur atom in even positions decreased hepatic and cardiac mitochondrial beta-oxidation and profoundly increased hepatic and cardiac TAG levels. The plasma TAG level was unchanged and the hepatic acyl-CoA oxidase activity increased. In contrast, thia FA with the sulfur atom in odd positions, especially 3-thia FA, tended to increase hepatic and cardiac FA oxidation and acyl-CoA oxidase and carnitine palmitoyltransferase-II activities, and decreased the plasma TAG levels. The effects seem to be related to differences in the catabolic rate of the thia FA. Differences between the two groups of acids were also observed with respect to the regulation of genes involved in FA transport and catabolism. Feeding experiments with 3- and 4-thia FA in combination indicated that the 4-thia FA partly attenuated the effects of the 3-thia FA on mitochondrial FA oxidation and the hepatic TAG level. In summary, the position of the sulfur atom in the alkyl chain, especially whether it is placed in the even or odd position, is crucial for the biological effect of the thia FA.