Early modulation of genes encoding peroxisomal and mitochondrial β-oxidation enzymes by 3-thia fatty acids

• Published in: Biochemical pharmacology Vol. 56; no. 12; pp. 1571 - 1582
• Main Authors: Vaagenes, Hege, Madsen, Lise, Asiedu, Daniel K, Lillehaug, Johan R, Berge, Rolf K
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 15.12.1998; Elsevier Science
• Subjects: 3-thia fatty acids; acid-soluble CoAs; Acyl-CoA Oxidase; Animals; Biological and medical sciences; Carnitine O-Palmitoyltransferase - biosynthesis; Carnitine O-Palmitoyltransferase - genetics; Carrier Proteins - biosynthesis; Carrier Proteins - genetics; Cell Fractionation; Cholesterol - blood; Dicarboxylic Acids - pharmacology; fatty acid composition; Fatty Acid Desaturases - biosynthesis; Fatty Acid Desaturases - genetics; Fatty Acid-Binding Protein 7; Fatty Acid-Binding Proteins; General and cellular metabolism. Vitamins; Liver - drug effects; Liver - enzymology; Male; Medical sciences; Microbodies - enzymology; Mitochondria - enzymology; mitochondrial and peroxisomal β-oxidation; mRNA; Myelin P2 Protein - biosynthesis; Myelin P2 Protein - genetics; Neoplasm Proteins; Nerve Tissue Proteins; Oxidoreductases - biosynthesis; Oxidoreductases - genetics; Oxidoreductases Acting on CH-CH Group Donors; Palmitic Acid - pharmacology; Pharmacology. Drug treatments; Phospholipids - blood; Rats; Rats, Wistar; RNA, Messenger - analysis; Sulfides - pharmacology; Time Factors; triglycerides; Triglycerides - blood; acid-soluble CoAs; mRNA; 3-thia fatty acids; mitochondrial and peroxisomal β-oxidation; triglycerides; fatty acid composition; Cell oxidation; Rat; Enzyme; Rodentia; Gene expression; Fatty acids; Intragastric administration; Liver function; Vertebrata; Mitochondria; Mammalia; Enzymatic activity; Animal; Modulation; Thioacid; Peroxisome; Biological effect; Mechanism of action
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/S0006-2952(98)00193-2

The aim of the present study was to elucidate the effects of a single dose of 3-thia fatty acids (tetradecylthioacetic acid and 3-thiadicarboxylic acid) over a 24-hr study period on the expression of genes related to peroxisomal and mitochondrial β-oxidation in liver of rats. The plasma triglyceride level decreased at 2–4 hr, 4–8 hr, and 8–24 hr, respectively, after a single dose of 150, 300, or 500 mg of 3-thia fatty acids/kg body weight. Four to eight hours after administration of 3-thia fatty acids, a several-fold-induced gene expression of peroxisomal multifunctional protein, fatty acyl-CoA oxidase (EC 1.3.3.6), fatty acid binding protein, and 2,4-dienoyl-CoA reductase (EC 1.3.1.43) resulted, concomitant with increased activity of 2,4-dienoyl-CoA reductase and fatty acyl-CoA oxidase. The expression of carnitine palmitoyltransferase-I and carnitine palmitoyltransferase-II increased at 2 and 4 hr, respectively, although at a smaller scale. In cultured hepatocytes, 3-thia fatty acids stimulated fatty acid oxidation after 4 hr, and this was both L-carnitine- and L-aminocarnitine-sensitive. The hepatic content of eicosapentaenoic acid and docosahexaenoic acid decreased throughout the study period. In contrast, the hepatic content of oleic acid tended to increase after 24 hr and was significantly increased after repeated administration of 3-thia fatty acids. Similarly, the expression of Δ 9-desaturase was unchanged during the 24-hr study, but increased after feeding for 5 days. To conclude, carnitine palmitoyltransferase-I expression seemed to be induced earlier than 2,4-dienoyl-CoA reductase and fatty acid binding protein, and not later than the peroxisomal fatty acyl-CoA oxidase. The expression of Δ 9-desaturase showed a more delayed response.