Metabolic Flexibility in Health and Disease

Goodpaster, Bret H.; Sparks, Lauren M.

doi:10.1016/j.cmet.2017.04.015

Cited by 995Adipose Tissue and MetabolismMetabolism, Diabetes, and CancerAdipokines, Inflammation, and Metabolic Diseases

Metabolic Flexibility in Health and Disease

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Goodpaster, Bret H., Sparks, Lauren M.·2017·Cell Metabolism

DOI 10.1016/j.cmet.2017.04.015PMC PMC5513193

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Abstract

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 cannot increase RER to the same extent as lean individuals.
“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
The “What is metabolic flexibility?” section describes metabolic inflexibility in obesity and type 2 diabetes in the context of fasting-to-insulin-stimulated fuel selection. The “Skeletal muscle drives fuel catabolism” section explains that insulin drives the normal shift toward glucose oxidation. Neither passage establishes the specific claim that both groups have a smaller increase in RER than lean individuals during insulin stimulation; the paper discusses respiratory quotient (RQ), not that comparison of RER changes. (LLM, conf=0.78)
Experimental — accuracy not yet measured
In the resting state, obese people have a higher RER than lean individuals, meaning a larger fraction of energy derives from carbohydrate oxidation, and this effect is more pronounced in T2DM.
“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
The section on metabolic inflexibility during exercise says people with obesity or type 2 diabetes have reduced fatty-acid oxidation under resting, fasted conditions. The white-adipose-tissue section explains that a higher RQ indicates greater reliance on carbohydrate oxidation. Neither passage establishes that resting RER is higher in obesity than in lean people, or that the difference is more pronounced in type 2 diabetes; page numbers are unavailable in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Metabolic flexibility is important for proper metabolic regulation.
“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
Previous work considered exercise-induced lipid oxidation as metabolic flexibility to lipid without accounting for lipid availability.
“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]
Diabetes is associated with impaired metabolic flexibility.
“As diabetes is associated with impaired metabolic flexibility [176]”
From Targeting Intramyocellular Lipids to Improve Aging Muscle Function (2025) · cites this paper as [176]

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Metabolic flexibility and insulin resistance
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Authors: Goodpaster, B. H., & Sparks, L. M.
Affiliations: Sanford Burnham Prebys Medical Discovery Institute (US)
Corresponding author: Goodpaster, Bret H.
ORCID: Goodpaster, Bret H.
Sparks, Lauren M.
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2017-05
Volume: 25
Issue: 5
Pages: 1027-1036
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2017.04.015
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 367 d)
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 › Adipose Tissue and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Epidemiology › 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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Metabolic Flexibility in Health and Disease

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