Cited by 173Metabolism, Diabetes, and CancerMuscle metabolism and nutritionAdipose Tissue and Metabolism

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

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Roepstorff, Carsten, Halberg, Nils, Hillig, Thore, Saha, Asish K., Ruderman, Neil B., Wojtaszewski, Jørgen F. P., Richter, Erik A., Kiens, Bente·2005·American Journal of Physiology-Endocrinology and Metabolism

Abstract

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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Crossref · 10.1152/ajpendo.00379.2004

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  • The reduction in intra-muscular free carnitine limits the ability of CPT-1 to transport long chain FA to the mitochondria.

    “Thus, the reduction in intra-muscular free carnitine limits the ability of CPT-1 to transport long chain FA to the mitochondria [157].”

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Authors
Roepstorff, C., Halberg, N., Hillig, T., Saha, A. K., Ruderman, N. B., Wojtaszewski, J. F. P., Richter, E. A., & Kiens, B.
Affiliations
University of Copenhagen (DK)
Venue
American Journal of Physiology-Endocrinology and Metabolism
Published
2005-01
Volume
288
Issue
1
Pages
E133-E142
ISSN
  • 0193-1849 (ISSN-L)
  • 1522-1555
OpenAlex
W2143035710
Cited by
173
References
50
Citations by year
2026: 1 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 5 · 2020: 5 · 2019: 7 · 2018: 6 · 2017: 8 · 2016: 7 · 2015: 9 · 2014: 15 · 2013: 9 · 2012: 12
FWCI
3.43
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • American Journal of Physiology-Endocrinology and Metabolism (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Keywords
fat oxidation, skeletal muscle, physical activity, malonyl-CoA, L-carnitine, acetyl-L-carnitine, acetyl-CoA carboxylase, muscle glycogen, low-carbohydrate diet, pyruvate dehydrogenase, acetyl-CoA, free carnitine
MeSH terms
Acetyl-CoA Carboxylase, Acetyl Coenzyme A, Acetylcarnitine, Adenylate Kinase, Adult, Carnitine, Dietary Carbohydrates, Fatty Acids, Glucose, Glycogen, Heart Rate, Humans, Insulin, Male, Malonyl Coenzyme A, Oxidation-Reduction, Pyruvate Dehydrogenase Complex, Exercise, Muscle, Skeletal

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