Abstract

Exercise activates muscle pyruvate dehydrogenase complex (PDC), but moderate intensity exercise fails to fully activate muscle PDC after high-fat diet [1]. We investigated whether maximal intensity exercise overcomes this inhibition. Quadriceps femoris muscle biopsy samples were obtained from healthy males at rest, and after 46 and 92 electrically-evoked maximal intermittent isometric contractions, which were preceded by 3 days of either low- (18%) or high- (69%) isocaloric dietary fat intake (LFD and HFD, respectively). The ratio of PDCa (active form) to total PDCt (fully activated) at rest was 50% less after HFD (0.32±0.01 vs 0.15±0.01; P<0.05). This ratio increased to 0.77±0.06 after 46 contractions (P<0.001) and to 0.98±0.07 after 92 contractions (P<0.001) in LFD. The corresponding values after HFD were less (0.54±0.06; P<0.01 and 0.70±0.07; P<0.01, respectively). Resting muscle acetyl-CoA and acetylcarnitine content was greater after HFD than LFD (both P<0.05), but their rate of accumulation in the former was reduced during contraction. Muscle lactate content after 92 contractions was 30% greater after HFD (P<0.05). Muscle force generation during contraction was no different between interventions, but HFD lengthened muscle relaxation time (P<0.05). Daily urinary total carnitine excretion after HFD was 2.5-fold greater than after LFD (P<0.01). A bout of maximal intense exercise did not overcome dietary fat-mediated inhibition of muscle pyruvate dehydrogenase complex activation, and was associated with greater muscle lactate accumulation, as a result of lower PDC flux, and increased muscle relaxation time.

Highlights

  • The mitochondrial membrane-bound enzyme pyruvate dehydrogenase complex (PDC)catalyses the irreversible decarboxylation of pyruvate to acetyl-CoA, and is thought to be the rate limiting step in carbohydrate (CHO) oxidation

  • We showed previously that the magnitude of muscle PDC activation correlates to the intensity of exercise transformation/activation of muscle PDC to PDCa is achieved within 74 s of intermittent electrically evoked maximal intensity isometric contraction [9] or within 10 min of moderate exercise (75%VO2max) [8] under conditions of habitual dietary intake

  • The results clearly demonstrate that electrically evoked maximal intensity isometric contraction was unable to rescue the impairment of PDC activation seen after 3 days of High-fat dietary intake (HFD) intervention vs the LFD intervention

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Summary

Introduction

The mitochondrial membrane-bound enzyme pyruvate dehydrogenase complex (PDC)catalyses the irreversible decarboxylation of pyruvate to acetyl-CoA, and is thought to be the rate limiting step in carbohydrate (CHO) oxidation. Voluntary dynamic and static (isometric) exercise and involuntary (i.e. electrically evoked) muscle contraction have been shown to transform to varying degrees the inactive (phosphorylated) form of PDC to its active (dephosphorylated) form (PDCa) in rodent skeletal muscle and heart [2,3,4], and in canine [5] and human skeletal muscle [6,7,8,9]. We showed previously that the magnitude of muscle PDC activation correlates to the intensity of exercise transformation/activation of muscle PDC to PDCa is achieved within 74 s of intermittent electrically evoked maximal intensity isometric contraction [9] or within 10 min of moderate exercise (75%VO2max) [8] under conditions of habitual dietary intake. Exercise activates muscle pyruvate dehydrogenase complex (PDC), but moderate intensity exercise fails to fully activate muscle PDC after high-fat diet [1].

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