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Malonyl-CoA and carnitine in regulation of fat oxidation in human skeletal muscle during exercise
Open accessAbstract
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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“Thus, the reduction in intra-muscular free carnitine limits the ability of CPT-1 to transport long chain FA to the mitochondria [157].”
From Regulation of Energy Substrate Metabolism in Endurance Exercise (2021) · cites this paper as [157]
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Self-citationContraction-induced Changes in Acetyl-CoA Carboxylase and 5′-AMP-activated Kinase in Skeletal Muscle
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Self-citationPark, H., Kaushik, V. K., Constant, S., Prentki, M., Przybytkowski, E., Ruderman, N. B., & Saha, A. K. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201692200 · Cited by 388
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- 10.1172/JCI0215715 · DOI
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Steinberg, G. R., & Kemp, B. E. (2009) · Physiological Reviews · doi:10.1152/physrev.00011.2008 · Cited by 1,672
Glatz, J. F. C., Luiken, J. J. F. P., & Bonen, A. (2010) · Physiological Reviews · doi:10.1152/physrev.00003.2009 · Cited by 776
CPT1A-mediated Fat Oxidation, Mechanisms, and Therapeutic Potential
Schlaepfer, I. R., & Joshi, M. (2020) · Endocrinology · doi:10.1210/endocr/bqz046 · Cited by 783
Dreyer, H. C., Fujita, S., Cadenas, J. G., Chinkes, D. L., Volpi, E., & Rasmussen, B. B. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.113175 · Cited by 570
AMPK and the biochemistry of exercise: implications for human health and disease
Richter, E. A., & Ruderman, N. B. (2009) · Biochemical Journal · doi:10.1042/bj20082055 · Cited by 481
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Metadata
- 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)
- ORCID
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- 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
- hybrid
- doi.org
- 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
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Health Sciences › Medicine › Physiology (medical) › 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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