PDH-E1alpha dephosphorylation and activation in human skeletal muscle during exercise: effect of intralipid infusion.
To investigate pyruvate dehydrogenase (PDH)-E1alpha subunit phosphorylation and whether free fatty acids (FFAs) regulate PDH activity, seven subjects completed two trials: saline (control) and intralipid/heparin (intralipid). Each infusion trial consisted of a 4-h rest followed by a 3-h two-legged knee extensor exercise at moderate intensity. During the 4-h resting period, activity of PDH in the active form (PDHa) did not change in either trial, yet phosphorylation of PDH-E1alpha site 1 (PDH-P1) and site 2 (PDH-P2) was elevated in the intralipid compared with the control trial. PDHa activity increased during exercise similarly in the two trials. After 3 h of exercise, PDHa activity remained elevated in the intralipid trial but returned to resting levels in the control trial. Accordingly, in both trials PDH-P1 and PDH-P2 decreased during exercise, and the decrease was more marked during intralipid infusion. Phosphorylation had returned to resting levels at 3 h of exercise only in the control trial. Thus, an inverse association between PDH-E1alpha phosphorylation and PDHa activity exists. Short-term elevation in plasma FFA at rest increases PDH-E1alpha phosphorylation, but exercise overrules this effect of FFA on PDH-E1alpha phosphorylation leading to even greater dephosphorylation during exercise with intralipid infusion than with saline.
Pilegaard
Henriette
H
August Krogh Building, Universitetsparken 13, 2100 Copenhagen Ø, Denmark. hpilegaard@aki.ku.dk
Birk
Jesper B
JB
Sacchetti
Massimo
M
Mourtzakis
Marina
M
Hardie
D Graham
DG
Stewart
Greg
G
Neufer
P Darrell
PD
Saltin
Bengt
B
van Hall
Gerrit
G
Wojtaszewski
Jorgen F P
JF
D000328:Adult; D018076:DNA, Complementary / Q000235:genetics; D004789:Enzyme Activation; D015444:Exercise / Q000502:physiology*; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D007262:Infusions, Intravenous; D007719:Knee Joint; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000201:enzymology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D010766:Phosphorylation; D030481:Pyruvate Dehydrogenase (Lipoamide) / Q000235:genetics* / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012146:Rest
D018076:DNA, Complementary; D005217:Fat Emulsions, Intravenous; D005230:Fatty Acids, Nonesterified; D012313:RNA; D006003:Glycogen; D030481:Pyruvate Dehydrogenase (Lipoamide); C065640:pyruvate dehydrogenase E1alpha subunit