PDH-E1alpha dephosphorylation and activation in human skeletal muscle during exercise: effect of intralipid infusion

TY - JOUR

T1 - PDH-E1alpha dephosphorylation and activation in human skeletal muscle during exercise

T2 - effect of intralipid infusion

AU - Pilegaard, Henriette

AU - Birk, Jesper Bratz

AU - Sacchetti, Massimo

AU - Mourtzakis, Marina

AU - Hardie, D. Graham

AU - Stewart, Greg

AU - Neufer, P. Darrell

AU - Saltin, Bengt

AU - Van Hall, Gerrit

AU - Wojtaszewski, Jørgen

N1 - PUF 2006 5200 022

PY - 2006

Y1 - 2006

N2 - To investigate pyruvate dehydrogenase (PDH)-E1a 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-E1a 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-E1a phosphorylation and PDHa activity exists. Short-term elevation in plasma FFA at rest increases PDH-E1a phosphorylation, but exercise overrules this effect of FFA on PDH-E1a phosphorylation leading to even greater dephosphorylation during exercise with intralipid infusion than with saline.

AB - To investigate pyruvate dehydrogenase (PDH)-E1a 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-E1a 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-E1a phosphorylation and PDHa activity exists. Short-term elevation in plasma FFA at rest increases PDH-E1a phosphorylation, but exercise overrules this effect of FFA on PDH-E1a phosphorylation leading to even greater dephosphorylation during exercise with intralipid infusion than with saline.

U2 - 10.2337/db06-0152

DO - 10.2337/db06-0152

M3 - Journal article

SN - 0012-1797

VL - 55

SP - 3020

EP - 3027

JO - Diabetes

JF - Diabetes

IS - 11

ER -