Long-term regulation of pyruvate dehydrogenase kinase by high-fat feeding. Experiments in vivo and in cultured cardiomyocytes.
The provision of the high-fat diet (47% of calories as fat) for 28 days evoked a significant decline in cardiac PDHa activity, together with marked increases in the activity of PDH kinase measured in isolated mitochondria and freshly-prepared cardiomyocytes from adult rats. Plasma insulin concentrations in fat-fed rats were not significantly different from control, but plasma NEFA concentrations were elevated. PDH kinase activity in cardiomyocytes from fat-fed rats fell substantially in culture (25 h). This decline was prevented by the inclusion of n-octanoate and DBcAMP in combination, but not individually, in the culture medium. The results are discussed in relation to the role for fatty acids and insulin in the long-term modulation of cardiac PDH kinase activity by high-fat feeding.
Orfali
K A
KA
Department of Biochemistry, Faculty of Basic Medical Sciences, Queen Mary and Westfield College, University of London, UK.
Fryer
L G
LG
Holness
M J
MJ
Sugden
M C
MC
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D004041:Dietary Fats / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006321:Heart / Q000187:drug effects; D006352:Heart Ventricles; D007328:Insulin / Q000097:blood; D009206:Myocardium / Q000201:enzymology*; D011494:Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011768:Pyruvate Dehydrogenase Complex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D013217:Starvation
D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011768:Pyruvate Dehydrogenase Complex; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D002118:Calcium