Sedentary behaviour is a key determinant of metabolic inflexibility

Rynders, Corey A.; Blanc, Stephane; DeJong, Nathan; Bessesen, Daniel H.; Bergouignan, Audrey

doi:10.1113/jp273282

Cited by 137Physical Activity and HealthDiabetes, Cardiovascular Risks, and LipoproteinsAdipokines, Inflammation, and Metabolic Diseases

Sedentary behaviour is a key determinant of metabolic inflexibility

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Rynders, Corey A., Blanc, Stephane, DeJong, Nathan, Bessesen, Daniel H., Bergouignan, Audrey·2018·The Journal of Physiology

DOI 10.1113/jp273282PMC PMC5899985

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Abstract

Metabolic flexibility is defined as the ability to adapt substrate oxidation rates in response to changes in fuel availability. The inability to switch between the oxidation of lipid and carbohydrate appears to be an important feature of chronic disorders such as obesity and type 2 diabetes. Laboratory assessment of metabolic flexibility has traditionally involved measurement of the respiratory quotient (RQ) by indirect calorimetry during the fasted to fed transition (e.g. mixed meal challenge) or during a hyperinsulinaemic-euglycaemic clamp. Under these controlled experimental conditions, 'metabolic inflexibility' is characterized by lower fasting fat oxidation (higher fasting RQ) and/or an impaired ability to oxidize carbohydrate during feeding or insulin-stimulated conditions (lower postprandial or clamp RQ). This experimental paradigm has provided fundamental information regarding the role of substrate oxidation in the development of obesity and insulin resistance. However, the key determinants of metabolic flexibility among relevant clinical populations remain unclear. Herein, we propose that habitual physical activity levels are a primary determinant of metabolic flexibility. We present evidence demonstrating that high levels of physical activity predict metabolic flexibility, while physical inactivity and sedentary behaviours trigger a state of metabolic 'inflexibility', even among individuals who meet physical activity recommendations. Furthermore, we describe alternative experimental approaches to studying the concept of metabolic flexibility across a range of activity and inactivity. Finally, we address the promising use of strategies that aim to reduce sedentary behaviours as therapy to improve metabolic flexibility and reduce weight gain risk.

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Physical inactivity is likely one of the primary causes of metabolic inflexibility.
“Physical inactivity is likely one of the primary causes of metabolic inflexibility (220, 221);”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [221]

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Authors: Rynders, C. A., Blanc, S., DeJong, N., Bessesen, D. H., & Bergouignan, A.
Affiliations: University of Colorado Anschutz (US)
Institut Pluridisciplinaire Hubert Curien, Université de Strasbourg CNRS Strasbourg France
Division of Endocrinology, Metabolism and Diabetes and Anschutz Health and Wellness Center, University of Colorado School of Medicine Aurora CO USA
Denver Health Medical Center (US)
Centre National de la Recherche Scientifique (FR)
Corresponding author: Bergouignan, Audrey
ORCID: Rynders, Corey A.
DeJong, Nathan
Bessesen, Daniel H.
Bergouignan, Audrey
Venue: The Journal of Physiology
Publisher: Wiley
Published: 2017-07-04
Volume: 596
Issue: 8
Pages: 1319-1330
ISSN: 0022-3751 (ISSN-L)
1469-7793
DOI: 10.1113/jp273282
PMC: PMC5899985
OpenAlex: W2618971909
Cited by: 137
References: 69
Citations by year: 2026: 9 · 2025: 20 · 2024: 10 · 2023: 16 · 2022: 24 · 2021: 18 · 2020: 16 · 2019: 8 · 2018: 14 · 2017: 2
FWCI: 1.34
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: The Journal of Physiology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion)
Funders: National Institute of Diabetes and Digestive and Kidney Diseases (K99DK100465, DK048520‐21, DK02935, DK62874, HL116276)
Topics: Health Sciences › Medicine › Physiology › Physical Activity and Health
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords: sedentary behavior, metabolic flexibility, physical activity, substrate oxidation, respiratory quotient, fat oxidation, carbohydrate oxidation, obesity, type 2 diabetes, insulin resistance, physical inactivity, weight gain, sedentary behavior reduction
MeSH terms: Energy Metabolism, Humans, Insulin Resistance, Exercise, Lipid Metabolism, Sedentary Behavior

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Sedentary behaviour is a key determinant of metabolic inflexibility

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