Malonyl-CoA and carnitine in regulation of fat oxidation in human skeletal muscle during exercise

Sep 24, 2004American journal of physiology. Endocrinology and metabolism

How Malonyl-CoA and Carnitine Control Fat Burning in Human Muscles During Exercise

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Abstract

Leg fat oxidation was 122% higher during exercise after a low-carbohydrate diet compared to a high-carbohydrate diet.

Alpha2-AMP-activated protein kinase (alpha2-AMPK) activity increased twice as much in the low-carbohydrate condition compared to the high-carbohydrate condition.
Phosphorylation of acetyl-CoA carboxylase (ACC)beta Ser221 was similar under both dietary conditions, increasing 6-fold.
Exercise reduced malonyl-CoA concentration by 13% in both dietary conditions.
Pyruvate dehydrogenase activity was higher in the high-carbohydrate condition compared to the low-carbohydrate condition.
In the high-carbohydrate condition, exercise increased acetyl-CoA and acetylcarnitine concentrations while decreasing free carnitine concentration.

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Intracellular mechanisms regulating fat oxidation were investigated in human skeletal muscle during exercise. Eight young, healthy, moderately trained men performed bicycle exercise (60 min, 65% peak O2 consumption) on two occasions, where they ingested either 1) a high-carbohydrate diet (H-CHO) or 2) a low-carbohydrate diet (L-CHO) before exercise to alter muscle glycogen content as well as to induce, respectively, low and high rates of fat oxidation. Leg fat oxidation was 122% higher during exercise in L-CHO than in H-CHO (P < 0.001). In keeping with this, the activity of alpha2-AMP-activated protein kinase (alpha2-AMPK) was increased twice as much in L-CHO as in H-CHO (P < 0.01) at 60 min of exercise. However, acetyl-CoA carboxylase (ACC)beta Ser221 phosphorylation was increased to the same extent (6-fold) under the two conditions. The concentration of malonyl-CoA was reduced 13% by exercise in both conditions (P < 0.05). Pyruvate dehydrogenase activity was higher during exercise in H-CHO than in L-CHO (P < 0.01). In H-CHO only, the concentrations of acetyl-CoA and acetylcarnitine were increased (P < 0.001), and the concentration of free carnitine was decreased (P < 0.01), by exercise. The data suggest that a decrease in the concentration of malonyl-CoA, secondary to alpha2-AMPK activation and ACC inhibition (by phosphorylation), contributes to the increase in fat oxidation observed at the onset of exercise regardless of muscle glycogen levels. They also suggest that, with high muscle glycogen, the availability of free carnitine may limit fat oxidation during exercise, due to its increased use for acetylcarnitine formation.

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Malonyl-CoA and carnitine in regulation of fat oxidation in human skeletal muscle during exercise

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