Fatty acid oxidation and related gene expression in heart depleted of carnitine by mildronate treatment in the rat.
The metabolic and genic effects induced by a 20-fold lowering of carnitine content in the heart were studied in mildronate-treated rats. In the perfused heart, the proportion of palmitate taken up then oxidized was 5-10% lower, while the triacylglycerol (TAG) formation was 100% greater than in controls. The treatment was shown to increase the maximal capacity of heart homogenates to oxidize palmitate, the mRNA level of carnitine palmitoyltransferase I (CPT-I) isoforms, the specific activity of CPT-I in subsarcolemmal mitochondria and the total carnitine content of isolated mitochondria. Concomitantly, the increased mRNA expression of lipoprotein lipase, fatty acid translocase and enzymes of TAG synthesis was associated with a 5- and 2-times increase in serum TAG and free fatty acid contents, respectively. The compartmentation of carnitine at its main functional location was expected to allow the increased CPT-I activity to ensure in vivo correct fatty acid oxidation rates. All the inductions related to fatty acid transport, oxidation and esterification most likely stem from the abundance of blood lipids providing cardiomyocytes with more fatty acids.
Degrace
Pascal
P
UPRES Lipides et Nutrition EA2422, Faculté des Sciences Gabriel, Université de Bourgogne, Dijon, France.
Demizieux
Laurent
L
Gresti
Joseph
J
Tsoko
Marcelline
M
André
Agnès
A
Demaison
Luc
L
Clouet
Pierre
P
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D002331:Carnitine / Q000378:metabolism*; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics; D004951:Esterification / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D066298:In Vitro Techniques; D008071:Lipoprotein Lipase / Q000235:genetics; D008297:Male; D008763:Methylhydrazines / Q000008:administration & dosage*; D008929:Mitochondria, Heart / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D019308:Palmitic Acid / Q000378:metabolism; D010477:Perfusion; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000096:biosynthesis
D002317:Cardiovascular Agents; D005227:Fatty Acids; D008763:Methylhydrazines; D012333:RNA, Messenger; D014280:Triglycerides; D019308:Palmitic Acid; C050147:3-(2,2,2-trimethylhydrazine)propionate; D002334:Carnitine O-Palmitoyltransferase; D008071:Lipoprotein Lipase; D002331:Carnitine