The role of ampk in controlling metabolism and mitochondrial biogenesis during exercise
Open accessAbstract
New Findings What is the topic of this review? The topic of this review is the metabolic effects of AMP‐activated protein kinase (AMPK) on glucose and fatty acid (FA) uptake, FA oxidation and mitochondrial biogenesis in skeletal muscle at rest and during exercise/muscle contractions. What advances does it highlight? This review describes recent studies examining the molecular mechanisms by which AMPK regulates muscle metabolism. It specifically discusses the role of exercise on acetyl‐CoA carboxylase and malonyl‐CoA in the regulation of FA oxidation. It also discusses the role of AMPK in regulating glucose and FA uptake during exercise. Finally, the review describes the interaction between AMPK, peroxisome proliferator‐activated receptor γ co‐activator‐1α and sirtuin 1 in controlling mitochondrial biogenesis. Insulin resistance is associated with defects in skeletal muscle fatty acid (FA) metabolism that contribute to the development of type 2 diabetes. Endurance exercise increases FA and glucose metabolism, muscle mitochondrial content and insulin sensitivity. In skeletal muscle, basal rates of FA oxidation are dependent on AMP‐activated protein kinase (AMPK) phosphorylation of acetyl‐CoA carboxylase 2, the rate‐limiting enzyme controlling the production of the metabolic intermediate malonyl‐CoA. Likewise, AMPK is essential for maintaining muscle mitochondrial content in untrained mice; effects that may be mediated through regulation of the peroxisome proliferator‐activated receptor γ co‐activator‐1α. However, the importance of AMPK in regulating glucose and FA uptake, FA oxidation and mitochondrial biogenesis during and following endurance exercise training is not fully understood. A better understanding of the mechanisms by which endurance exercise regulates substrate utilization and mitochondrial biogenesis may lead to improved therapeutic and preventative strategies for the treatment of insulin resistance and type 2 diabetes.
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AMPK is essential for endurance exercise.
“AMPK is essential for endurance exercise [61].”
From Regulation of Energy Substrate Metabolism in Endurance Exercise (2021) · cites this paper as [61]
AMPK increases fatty-acid oxidation by inhibiting ACC2 through phosphorylation.
“Eventually, AMPK further increases fatty-acid oxidation by inhibiting acetyl-CoA carboxylase 2 (ACC2) through phosphorylation (Figure 2).”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [46]
A decrease in ACC activity reduces the levels of intracellular malonyl-CoA, an allosteric inhibitor of CPT1, allowing CPT1 to transfer long-chain fatty acids into mitochondria for oxidation.
“A decrease in ACC activity reduces the levels of intracellular malonyl-CoA, an allosteric inhibitor of CPT1. Hence, CPT1 can assume the transfer of long-chain fatty acids from the cytosol into the mitochondria, where they are oxidized [45,46].”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [46]
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- Authors
- Marcinko, K., & Steinberg, G. R.
- Affiliations
- McMaster University (CA)
- Corresponding author
- Steinberg, Gregory R.
- Venue
- Experimental Physiology
- Publisher
- Wiley
- Published
- 2014-11-03
- Volume
- 99
- Issue
- 12
- Pages
- 1581-1585
- ISSN
- 0958-0670 (ISSN-L)
- 1469-445X
- OpenAlex
- W1528807955
- Cited by
- 92
- References
- 28
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 8 · 2022: 8 · 2021: 8 · 2020: 11 · 2019: 14 · 2018: 5 · 2017: 11 · 2016: 8 · 2015: 5 · 2014: 1
- FWCI
- 3.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Experimental Physiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Keywords
- AMPK, physical activity, skeletal muscle metabolism, mitochondrial biogenesis, fatty acid oxidation, glucose uptake, fatty acid uptake, acetyl-CoA carboxylase 2, malonyl-CoA, PGC-1α, SIRT1, insulin resistance, type 2 diabetes, endurance training
- MeSH terms
- Adenylate Kinase, Animals, Biological Transport, Glucose, Humans, Mitochondria, Muscle, Physical Conditioning, Animal, Signal Transduction, Exercise, Muscle, Skeletal, Mitochondrial Turnover
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