Regulation of carnitine palmitoyltransferase (CPT) I during fasting in rainbow trout (Oncorhynchus mykiss) promotes increased mitochondrial fatty acid oxidation.
Periods of fasting, in most animals, are fueled principally by fatty acids, and changes in the regulation of fatty acid oxidation must exist to meet this change in metabolic substrate use. We examined the regulation of carnitine palmitoyltransferase (CPT) I, to help explain changes in mitochondrial fatty acid oxidation with fasting. After fasting rainbow trout (Oncorhynchus mykiss) for 5 wk, the mitochondria were isolated from red muscle and liver to determine (1) mitochondrial fatty acid oxidation rate, (2) CPT I activity and the concentration of malonyl-CoA needed to inhibit this activity by 50% (IC(50)), (3) mitochondrial membrane fluidity, and (4) CPT I (all five known isoforms) and peroxisome proliferator-activated receptor (PPARα and PPARβ) mRNA levels. Fatty acid oxidation in isolated mitochondria increased during fasting by 2.5- and 1.75-fold in liver and red muscle, respectively. Fasting also decreased sensitivity of CPT I to malonyl-CoA (increased IC(50)), by two and eight times in red muscle and liver, respectively, suggesting it facilitates the rate of fatty acid oxidation. In the liver, there was also a significant increase CPT I activity per milligram mitochondrial protein and in whole-tissue PPARα and PPARβ mRNA levels. However, there were no changes in mitochondrial membrane fluidity in either tissue, indicating that the decrease in CPT I sensitivity to malonyl-CoA is not due to bulk fluidity changes in the membrane. However, there were significant differences in CPT I mRNA levels during fasting. Overall, these data indicate some important changes in the regulation of CPT I that promote the increased mitochondrial fatty acid oxidation that occurs during fasting in trout.
Department of Biology, McMaster University, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada. am2023@cam.ac.uk
Andrea J
AJ
Morash
Grant B
GB
McClelland
D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism*; D002950:Citrate (si)-Synthase / Q000378:metabolism; D005215:Fasting / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D008316:Malonyl Coenzyme A / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism*; D008931:Mitochondria, Muscle / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000502:physiology; D017686:Oncorhynchus mykiss / Q000378:metabolism*; D010084:Oxidation-Reduction; D011897:Random Allocation
D005227:Fatty Acids; D008316:Malonyl Coenzyme A; D002334:Carnitine O-Palmitoyltransferase; D002950:Citrate (si)-Synthase