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Metabolic Flexibility in Health and Disease
Open accessAbstract
Metabolic flexibility is the ability to respond or adapt to conditional changes in metabolic demand. This broad concept has been propagated to explain insulin resistance and mechanisms governing fuel selection between glucose and fatty acids, highlighting the metabolic inflexibility of obesity and type 2 diabetes. In parallel, contemporary exercise physiology research has helped to identify potential mechanisms underlying altered fuel metabolism in obesity and diabetes. Advances in "omics" technologies have further stimulated additional basic and clinical-translational research to further interrogate mechanisms for improved metabolic flexibility in skeletal muscle and adipose tissue with the goal of preventing and treating metabolic disease.
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“during insulin stimulation, obese individuals and patients with T2DM are not able to increase the RER value to the same extent as lean individuals”
From Effect of Exercise Training on Fat Loss—Energetic Perspectives and the Role of Improved Adipose Tissue Function and Body Fat Distribution (2021) · cites this paper as Goodpaster and Sparks, 2017
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“In the resting state, obese people have a higher RER value when compared with lean individuals, meaning a larger fraction of the energy expended derives from carbohydrate oxidation, an effect that is even more pronounced in patients with T2DM”
From Effect of Exercise Training on Fat Loss—Energetic Perspectives and the Role of Improved Adipose Tissue Function and Body Fat Distribution (2021) · cites this paper as Goodpaster and Sparks, 2017
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In the citing paper
“Metabolic flexibility, the ability to switch between fat and carbohydrate oxidation with varying energy requirements seems to be important for proper metabolic regulation”
From Effect of Exercise Training on Fat Loss—Energetic Perspectives and the Role of Improved Adipose Tissue Function and Body Fat Distribution (2021) · cites this paper as Goodpaster and Sparks, 2017
In the citing paper
“MetFlex-lip during exercise has been considered previously as the level of exercise-induced lipid oxidation, without considering lipid availability (13).”
From Metabolic flexibility to lipid availability during exercise is enhanced in individuals with high insulin sensitivity (2018) · cites this paper as [13]
In the citing paper
“As diabetes is associated with impaired metabolic flexibility [176]”
From Targeting Intramyocellular Lipids to Improve Aging Muscle Function (2025) · cites this paper as [176]
In the citing paper
“As discussed previously, metabolic flexibility relies on the action of insulin and glucagon major regulators of glucose metabolism in response to dietary stage (107) (see “Feeding/fasting”, “Biochemical transition between feeding and fasting”, and “Prolonged fasting and caloric/dietary restriction”).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [107]
In the citing paper
“great progress has been made over the past few decades to understand its underpinnings”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [107]
In the citing paper
“the body readily shifts between metabolic fuels during carbohydrate restriction to maintain energy and blood glucose”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [37]
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Metadata
- Authors
- Goodpaster, B. H., & Sparks, L. M.
- Affiliations
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Corresponding author
- Goodpaster, Bret H.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2017-05
- Volume
- 25
- Issue
- 5
- Pages
- 1027-1036
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC5513193
- OpenAlex
- W2611848952
- Cited by
- 995
- References
- 129
- Citations by year
- 2026: 150 · 2025: 131 · 2024: 89 · 2023: 126 · 2022: 138 · 2021: 133 · 2020: 106 · 2019: 72 · 2018: 42 · 2017: 6
- FWCI
- 7.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- American Diabetes Association
- Topics
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- metabolic flexibility, insulin resistance, fuel selection, glucose metabolism, fatty acid oxidation, obesity, type 2 diabetes, skeletal muscle, adipose tissue, exercise physiology, metabolic disorders
- MeSH terms
- Adipose Tissue, Animals, Diabetes Mellitus, Type 2, Energy Metabolism, Exercise Therapy, Fasting, Fatty Acids, Glucose, Humans, Insulin Resistance, Obesity, Rest, Exercise, Muscle, Skeletal, Caloric Restriction, Metabolic Networks and Pathways, Metabolomics, Metabolome
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