Your mitochondria are what you eat: a high-fat or a high-sucrose diet eliminates metabolic flexibility in isolated mitochondria from rat skeletal muscle
Open accessAbstract
Abstract Extreme diets consisting of either high fat (HF) or high sucrose (HS) may lead to insulin resistance in skeletal muscle, often associated with mitochondrial dysfunction. However, it is not known if these diets alter normal interactions of pyruvate and fatty acid oxidation at the level of the mitochondria. Here, we report that rat muscle mitochondria does show the normal Randle‐type fat‐carbohydrate interaction seen in vivo. The mechanism behind this metabolic flexibility at the level of the isolated mitochondria is a regulation of the flux‐ratio: pyruvate dehydrogenase (PDH)/β‐oxidation to suit the actual substrate availability, with the PDH flux as the major point of regulation. We further report that this regulatory mechanism of carbohydrate‐fat metabolic interaction surprisingly is lost in mitochondria obtained from animals exposed for 12 weeks to a HF‐ or a HS diet as compared to rats given a normal chow diet. The mechanism seems to be a loss of the PDH flux decrease seen in controls, when fatty acid is supplied as substrate in addition to pyruvate, and vice versa for the supply of pyruvate as substrate to mitochondria oxidizing fatty acid. Finally, we report that the calculated TCA flux in the isolated mitochondria under these circumstances shows a significant reduction (~50%) after the HF diet and an even larger reduction (~75%) after the HS diet, compared with the chow group. Thus, it appears that obesogenic diets as those applied here have major influence on key metabolic performance of skeletal muscle mitochondria.
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Isolated skeletal muscle mitochondria from rats fed high-sugar or high-fat diets show reduced metabolic flexibility.
“Recently, isolated skeletal muscle mitochondria from rats fed high-sugar or high-fat diets showed reduced metabolic flexibility, indicating that substrate preference is independent of cytosolic-mitochondrial communication and in fact a consequence of inherent mitochondrial biochemical network interactions (92, 93).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [92]
Substrate preference is independent of cytosolic-mitochondrial communication and is a consequence of inherent mitochondrial biochemical network interactions.
“Recently, isolated skeletal muscle mitochondria from rats fed high-sugar or high-fat diets showed reduced metabolic flexibility, indicating that substrate preference is independent of cytosolic-mitochondrial communication and in fact a consequence of inherent mitochondrial biochemical network interactions (92, 93).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [92]
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- Authors
- Jørgensen, W., Rud, K. A., Mortensen, O. H., Frandsen, L., Grunnet, N., & Quistorff, B.
- Affiliations
- University of Copenhagen (DK)
- Corresponding author
- Quistorff, Bjørn
- Venue
- Physiological Reports
- Publisher
- Wiley
- Published
- 2017-03
- Volume
- 5
- Issue
- 6
- ISSN
- 2051-817X (ISSN-L)
- PMC
- PMC5371568
- OpenAlex
- W2599614834
- Cited by
- 48
- References
- 27
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 4 · 2023: 2 · 2022: 1 · 2021: 7 · 2020: 14 · 2019: 5 · 2018: 4 · 2017: 3
- FWCI
- 2.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Physiological Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- Funders
- Det Frie Forskningsråd (4004‐00315B)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- metabolic flexibility, skeletal muscle mitochondria, high-fat diet, high-sucrose diet, pyruvate dehydrogenase, fatty acid beta-oxidation, TCA cycle flux, insulin resistance, mitochondrial dysfunction, obesogenic diet
- MeSH terms
- Animals, Dietary Fats, Fatty Acids, Insulin Resistance, Mitochondria, Muscle, Oxidation-Reduction, Pyruvate Dehydrogenase Complex, Rats, Wistar, Muscle, Skeletal, Dietary Sucrose, Rats, Diet, High-Fat
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