Metabolic flexibility and obesity in children and youth

Aucouturier, J.; Duché, P.; Timmons, B. W.

doi:10.1111/j.1467-789x.2010.00812.x

Cited by 43Diabetes, Cardiovascular Risks, and LipoproteinsAdipose Tissue and MetabolismAdipokines, Inflammation, and Metabolic Diseases

Metabolic flexibility and obesity in children and youth

Open access

Aucouturier, J., Duché, P., Timmons, B. W.·2011·Obesity Reviews

DOI 10.1111/j.1467-789x.2010.00812.x

Open this paper in CoChat — free account Open PDF

Abstract

The concept of metabolic flexibility describes the ability of skeletal muscle to switch between the oxidation of lipid as a fuel during fasting periods to the oxidation of carbohydrate during insulin stimulated period. Alterations in energy metabolism in adults with obesity, insulin resistance and/or type 2 diabetes induce a state of impaired metabolic flexibility, or metabolic inflexibility. Despite the increase in the prevalence of type 2 diabetes in obese children and youth, less is known about the factors involved in the development of metabolic inflexibility in the paediatric population. Metabolic flexibility is conditioned by nutrient partitioning in response to feeding, substrate mobilization and delivery to skeletal muscle during fasting or exercising condition, and skeletal muscle oxidative capacity. Our aim in this review was to identify among these factors those making obese children at risk of metabolic inflexibility. The development of ectopic rather than peripheral fat storage appears to be a factor strongly linked with a reduced metabolic flexibility. Tissue growth and maturation are determinants of impaired energy metabolism later in life but also as a promising way to reverse metabolic inflexibility given the plasticity of many tissues in youth. Finally, we have attempted to identify perspectives for future investigations of metabolic flexibility in obese children that will improve our understanding of the genesis of metabolic diseases associated with obesity.

Integrity signals

Registry

Crossref · 10.1111/j.1467-789x.2010.00812.x

Cites

62 of 62 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Obesity is predominantly associated with elevated levels of plasma free fatty acids.
“Obesity is predominantly associated with elevated levels of plasma free fatty acids (141).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [141]

Abdominal obesity and metabolic syndrome
Després, J.-P., & Lemieux, I. (2006) · Nature · doi:10.1038/nature05488 · Cited by 4,354 · see citing works
Mechanisms of fatty acid-induced inhibition of glucose uptake.
Boden, G., Chen, X., Ruiz, J., White, J. V., & Rossetti, L. (1994) · Journal of Clinical Investigation · doi:10.1172/jci117252 · Cited by 3,702 · see citing works
Cellular mechanisms of insulin resistance
Shulman, G. I. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10583 · Cited by 2,714 · see citing works
Mitochondrial Overload and Incomplete Fatty Acid Oxidation Contribute to Skeletal Muscle Insulin Resistance
Koves, T. R., Ussher, J. R., Noland, R. C., Slentz, D., Mosedale, M., Ilkayeva, O., Bain, J., Stevens, R., Dyck, J. R. B., Newgard, C. B., et al. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2007.10.013 · Cited by 1,990 · see citing works
ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism
Berg, A. H., Combs, T. P., & Scherer, P. E. (2002) · Trends in Endocrinology and Metabolism · doi:10.1016/s1043-2760(01)00524-0 · Cited by 1,211 · see citing works
Skeletal muscle fatty acid metabolism in association with insulin resistance, obesity, and weight loss
Kelley, D. E., Goodpaster, B., Wing, R. R., & Simoneau, J.-A. (1999) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1999.277.6.e1130 · Cited by 1,096 · see citing works
Emerging epidemic of type 2 diabetes in youth
Rosenbloom, A. L., Joe, J. R., Young, R. S., & Winter, W. E. (1999) · Diabetes Care · doi:10.2337/diacare.22.2.345 · Cited by 1,019 · cited 1× · see citing works
“Despite the increase in the prevalence of obesity in children and youth over the last decades (2), much less is known about the link between metabolic flexibility and the development of insulin resistance in the paediatric population.”
Background
Fuel selection in human skeletal muscle in insulin resistance: a reexamination.
Kelley, D. E., & Mandarino, L. J. (2000) · Diabetes · doi:10.2337/diabetes.49.5.677 · Cited by 1,017 · see citing works
Deficiency of subsarcolemmal mitochondria in obesity and type 2 diabetes
Ritov, V. B., Menshikova, E. V., He, J., Ferrell, R. E., Goodpaster, B. H., & Kelley, D. E. (2005) · Diabetes · doi:10.2337/diabetes.54.1.8 · Cited by 887 · see citing works
Plasma Acylcarnitine Profiles Suggest Incomplete Long-Chain Fatty Acid β-Oxidation and Altered Tricarboxylic Acid Cycle Activity in Type 2 Diabetic African-American Women
Adams, S. H., Hoppel, C. L., Lok, K. H., Zhao, L., Wong, S. W., Minkler, P. E., Hwang, D. H., Newman, J. W., & Garvey, W. T. (2009) · The Journal of Nutrition · doi:10.3945/jn.108.103754 · Cited by 598 · see citing works
Metabolic flexibility and insulin resistance
Galgani, J. E., Moro, C., & Ravussin, E. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90558.2008 · Cited by 532 · cited 1× · see citing works
“However, metabolic flexibility to lipid is also important because the ability to adapt fat utilization to availability determines the accumulation of fat in ectopic fat depots and the subsequent development of insulin resistance (54).”
Background
Prediabetes in obese youth: a syndrome of impaired glucose tolerance, severe insulin resistance, and altered myocellular and abdominal fat partitioning.
Weiss, R., Dufour, S., Taksali, S. E., Tamborlane, W., Petersen, K., Bonadonna, R., Boselli, L., Barbetta, G., Allen, K., Rife, F., et al. (2003) · The Lancet · doi:10.1016/s0140-6736(03)14364-4 · Cited by 523 · see citing works
Excess Lipid Availability Increases Mitochondrial Fatty Acid Oxidative Capacity in Muscle
Turner, N., Bruce, C. R., Beale, S. M., Hoehn, K. L., So, T., Rolph, M. S., & Cooney, G. J. (2007) · Diabetes · doi:10.2337/db07-0093 · Cited by 520 · see citing works
Markers of capacity to utilize fatty acids in human skeletal muscle: relation to insulin resistance and obesity and effects of weight loss.
Simoneau, J., Veerkamp, J. H., Turcotte, L. P., & Kelley, D. E. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.14.2051 · Cited by 491 · see citing works
Assessment of Skeletal Muscle Triglyceride Content by 1H Nuclear Magnetic Resonance Spectroscopy in Lean and Obese Adolescents
Sinha, R., Dufour, S., Petersen, K. F., LeBon, V., Enoksson, S., Ma, Y.-Z., Savoye, M., Rothman, D. L., Shulman, G. I., & Caprio, S. (2002) · Diabetes · doi:10.2337/diabetes.51.4.1022 · Cited by 489 · see citing works
Interaction between glucose and free fatty acid metabolism in human skeletal muscle.
Kelley, D. E., Mokáň, M., Simoneau, J. A., & Mandarino, L. J. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116603 · Cited by 481 · see citing works
Central overweight and obesity in British youth aged 11–16 years: cross sectional surveys of waist circumference
McCarthy, H. D., Ellis, S. M., & Cole, T. J. (2003) · BMJ · doi:10.1136/bmj.326.7390.624 · Cited by 445 · see citing works
Obesity in Children and Adolescents
Cali, A. M. G., & Caprio, S. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-1363 · Cited by 444 · see citing works
Puberty decreases insulin sensitivity
Bloch, C., Clemons, P., & Sperling, M. A. (1987) · The Journal of Pediatrics · doi:10.1016/s0022-3476(87)80522-x · Cited by 367 · see citing works
Adiponectin in Youth
Bacha, F. F., Saad, R. J., Gungor, N., & Arslanian, S. A. (2004) · Diabetes Care · doi:10.2337/diacare.27.2.547 · Cited by 278 · see citing works
The metabolic consequences of childhood obesity
Weiss, R., & Caprio, S. (2005) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2005.04.009 · Cited by 278 · see citing works
Increased intramuscular lipid storage in the insulin-resistant and endurance-trained state
van Loon, L. J. C., & Goodpaster, B. H. (2006) · Pflügers Archiv · doi:10.1007/s00424-005-1509-0 · Cited by 232 · see citing works
Failure to increase lipid oxidation in response to increasing dietary fat content in formerly obese women.
Astrup, A., Buemann, B., Christensen, N. J., & Toubro, S. (1994) · American Journal of Physiology · doi:10.1152/ajpendo.1994.266.4.e592 · Cited by 231 · see citing works
Fat content in individual muscle fibers of lean and obese subjects.
Malenfant, P., Joanisse, D., Thériault, R., Goodpaster, B., Kelley, D., & Simoneau, J.-A. (2001) · International Journal of Obesity · doi:10.1038/sj.ijo.0801733 · Cited by 227 · see citing works
Exercise Alone Reduces Insulin Resistance in Obese Children Independently of Changes in Body Composition
Bell, L. M., Watts, K., Siafarikas, A., Thompson, A. M., Ratnam, N., Bulsara, M. K., Finn, J., O’Driscoll, G., GREEN, D. J., Jones, T. W., et al. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-0779 · Cited by 220 · see citing works
Association between the Insulin Resistance of Puberty and the Insulin-Like Growth Factor-I/Growth Hormone Axis
Moran, A., Jacobs, D. R., Steinberger, J., Cohen, P., Hong, C.-P., Prineas, R. J., & Sinaiko, A. R. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-020517 · Cited by 204 · see citing works
Insulin Resistance in Adolescents with Type 2 Diabetes Is Associated with Impaired Exercise Capacity
Nadeau, K. J., Zeitler, P. S., Bauer, T. A., Brown, M. S., Dorosz, J. L., Draznin, B., Reusch, J. E. B., & Regensteiner, J. G. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-2844 · Cited by 196 · see citing works
Relationship Between Body Fat Mass and Free Fatty Acid Kinetics in Men and Women
Mittendorfer, B., Magkos, F., Fabbrini, E., Mohammed, B. S., & Klein, S. (2009) · Obesity · doi:10.1038/oby.2009.224 · Cited by 192 · see citing works
Rapid impairment of skeletal muscle glucose transport/phosphorylation by free fatty acids in humans.
Roden, M., Krššák, M., Stingl, H., Gruber, S., Hofer, A., Fürnsinn, C., Moser, E., & Waldhäusl, W. K. (1999) · Diabetes · doi:10.2337/diabetes.48.2.358 · Cited by 189 · see citing works
Youth Type 2 Diabetes
Gungor, N., Bacha, F., Saad, R., Janosky, J., & Arslanian, S. (2005) · Diabetes Care · doi:10.2337/diacare.28.3.638 · Cited by 186 · see citing works
Association of physical activity with insulin sensitivity in children
Schmitz, K., Jacobs, D. R., Hong, C. P., Steinberger, J., Moran, A., & Sinaiko, A. R. (2002) · International Journal of Obesity · doi:10.1038/sj.ijo.0802137 · Cited by 184 · see citing works
Skeletal muscle “mitochondrial deficiency” does not mediate insulin resistance
Holloszy, J. O. (2009) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.2008.26717c · Cited by 175 · see citing works
Effects of Obesity on Substrate Utilization during Exercise
Goodpaster, B. H., Wolfe, R. R., & Kelley, D. E. (2002) · Obesity Research · doi:10.1038/oby.2002.78 · Cited by 169 · see citing works
Lipid peroxidation in skeletal muscle of obese as compared to endurance-trained humans: a case of good vs. bad lipids?
Russell, A. P., Gastaldi, G., Bobbioni-Harsch, E., Arboit, P., Gobelet, C., Dériaz, O., Golay, A., Witztum, J. L., & Giacobino, J.-P. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)00875-5 · Cited by 166 · see citing works
The “Obese Insulin-Sensitive” Adolescent: Importance of Adiponectin and Lipid Partitioning
Weiss, R., Taksali, S. E., Dufour, S., Yeckel, C. W., Papademetris, X., Cline, G. W., Tamborlane, W. V., Dziura, J., Shulman, G. I., & Caprio, S. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-2305 · Cited by 161 · see citing works
Metabolic Flexibility in Response to Glucose Is Not Impaired in People With Type 2 Diabetes After Controlling for Glucose Disposal Rate
Galgani, J. E., Heilbronn, L. K., Azuma, K., Kelley, D. E., Albu, J. B., Pi-Sunyer, X., Smith, S. R., Ravussin, E., & and the Look AHEAD Adipose Research Group (2008) · Diabetes · doi:10.2337/db08-0043 · Cited by 133 · see citing works
Muscle-Specific Adaptations, Impaired Oxidative Capacity and Maintenance of Contractile Function Characterize Diet-Induced Obese Mouse Skeletal Muscle
Shortreed, K. E., Krause, M. P., Huang, J. H., Dhanani, D., Moradi, J., Ceddia, R. B., & Hawke, T. J. (2009) · PLoS ONE · doi:10.1371/journal.pone.0007293 · Cited by 131 · see citing works
Are Obesity-Related Metabolic Risk Factors Modulated by the Degree of Insulin Resistance in Adolescents?
Bacha, F. F., Saad, R. J., Gungor, N., & Arslanian, S. A. (2006) · Diabetes Care · doi:10.2337/dc06-0581 · Cited by 127 · see citing works
Lifestyle intervention in obese children with non-alcoholic fatty liver disease: 2-year follow-up study
Reinehr, T., Schmidt, C., Toschke, A. M., & Andler, W. (2009) · Archives of Disease in Childhood · doi:10.1136/adc.2008.143594 · Cited by 124 · see citing works
Co-existence of severe insulin resistance and hyperinsulinaemia in pre-adolescent obese children
Caprio, S., Bronson, M. L., Sherwin, R. S., Rife, F., & Tamborlane, W. V. (1996) · Diabetologia · doi:10.1007/s001250050603 · Cited by 122 · see citing works
Fat and carbohydrate balances during adaptation to a high-fat diet
Smith, S. R., de Jonge, L., Zachwieja, J. J., Roy, H. J., Nguyen, T., Rood, J. C., WINDHAUSER, M. M., & Bray, G. A. (2000) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/71.2.450 · Cited by 120 · see citing works
Insulin resistance and whole body energy homeostasis in obese adolescents with fatty liver disease
Perseghin, G., Bonfanti, R., Magni, S., Lattuada, G., COBELLI, F. D., Canu, T., Esposito, A., Scifo, P., Ntali, G., Costantino, F., et al. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00017.2006 · Cited by 112 · see citing works
The endocrine response and substrate utilization during exercise in children and adolescents
Riddell, M. C. (2008) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00031.2008 · Cited by 111 · see citing works
Reduced exercise-associated response of the GH-IGF-I axis and catecholamines in obese children and adolescents
Eliakim, A., Nemet, D., Zaldivar, F. P., McMurray, R. G., Culler, F. L., Galassetti, P. R., & Cooper, D. M. (2005) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01072.2005 · Cited by 98 · see citing works
Skeletal Muscle Triglycerides
Kelley, D. E. (2002) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2002.tb04271.x · Cited by 97 · see citing works
Skeletal muscle triglycerides: an aspect of regional adiposity and insulin resistance.
Kelley, D. E. (2002) · PubMed · Cited by 84 · see citing works
Effects of insulin resistance on substrate utilization during exercise in overweight women
Braun, B., Sharoff, C., Chipkin, S. R., & Beaudoin, F. (2004) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00231.2004 · Cited by 84 · see citing works
Effects of Dietary Macronutrient Content on Glucose Metabolism in Children
Sunehag, A. L., TOFFOLO, G. M., Treuth, M. S., Butte, N. F., Cobelli, C., Bier, D. M., & Haymond, M. W. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-020674 · Cited by 84 · see citing works
Weight Loss Reduces Liver Fat and Improves Hepatic and Skeletal Muscle Insulin Sensitivity in Obese Adolescents
Vitola, B. E., Deivanayagam, S., Stein, R. I., Mohammed, B. S., Magkos, F., Kirk, E. P., & Klein, S. (2009) · Obesity · doi:10.1038/oby.2009.171 · Cited by 81 · see citing works
Carbohydrate balance predicts weight and fat gain in adults
Eckel, R. H., Hernandez, T. L., Bell, M. L., Weil, K. M., Shepard, T. Y., Grunwald, G. K., Sharp, T. A., Francis, C. C., & Hill, J. O. (2006) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/83.4.803 · Cited by 72 · see citing works
Influence of age and pubertal status on substrate utilization during exercise with and without carbohydrate intake in healthy boys
Timmons, B. W., Bar‐Or, O., & Riddell, M. C. (2007) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/h07-004 · Cited by 69 · see citing works
Self-citation
Carbohydrate balance and body-weight regulation
Flatt, J. P. (1996) · Proceedings of The Nutrition Society · doi:10.1079/pns19960041 · Cited by 55 · see citing works
Effects of Dietary Macronutrient Intake on Insulin Sensitivity and Secretion and Glucose and Lipid Metabolism in Healthy, Obese Adolescents
Sunehag, A. L., TOFFOLO, G. M., Campioni, M., Bier, D. M., & Haymond, M. W. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-0626 · Cited by 52 · see citing works
Optimizing fat oxidation through exercise in severely obese Caucasian adolescents
Lazzer, S., Busti, C., Agosti, F., Col, A. D., Pozzo, R., & Sartório, A. (2007) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2007.02929.x · Cited by 50 · see citing works
Effect of insulin on glycerol production in obese adolescents
Robinson, C., Tamborlane, W. V., Maggs, D. G., Enoksson, S., Sherwin, R. S., Silver, D., Shulman, G. I., & Caprio, S. (1998) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1998.274.4.e737 · Cited by 49 · see citing works
Comparison of the Type of Substrate Oxidation During Exercise Between Pre and Post Pubertal Markedly Obese Boys
Brandou, F., Savy-Pacaux, A., Marie, J., Brun, J. ‐., & Mercier, J. G. (2006) · International Journal of Sports Medicine · doi:10.1055/s-2005-865751 · Cited by 46 · see citing works
Techniques for the measurement of white adipose tissue metabolism: a practical guide.
Arner, P. (1995) · PubMed · Cited by 42 · see citing works
Responses of Lipolysis and Salivary Cortisol to Food Intake and Physical Activity in Lean and Obese Children
Hershberger, A. M., McCammon, M. R., Garry, J. P., Mahar, M. T., & Hickner, R. C. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031144 · Cited by 34 · see citing works
Increased Insulin Resistance in Obese Children Who Have Both 972 IRS-1 and 1057 IRS-2 Polymorphisms
Fur, S. L., Stunff, C. L., & Bougneres, P. F. (2002) · Diabetes · doi:10.2337/diabetes.51.2007.s304 · Cited by 32 · see citing works
Whole-body protein turnover and resting energy expenditure in obese, prepubertal children2
Schutz, Y., Rueda-Maza, C. M., Zaffanello, M., & Maffeis, C. (1999) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/69.5.857 · Cited by 32 · see citing works
Insulin sensitivity in physically fit and unfit children of parents with Type 2 diabetes
Ahn, C. W., Song, Y. D., Nam, J. H., Kim, D. M., Woo, S. O., Park, S., Cha, B. S., Lim, S. K., Kim, K. R., Lee, J. H., et al. (2003) · Diabetic Medicine · doi:10.1046/j.1464-5491.2003.01049.x · Cited by 21 · see citing works
Effets de la puberté sur la balance glucido-lipidique lors de l’exercice de l’enfant obèse
Zunquin, G., Theunynck, D., Sesboüé, B., Arhan, P., & Bouglé, D. L. (2006) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/h06-015 · Cited by 15 · see citing works

Flagged first, then by citations

Sorted by citations

Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease
Smith, R. L., Soeters, M. R., Wüst, R. C. I., & Houtkooper, R. H. (2018) · Endocrine Reviews · doi:10.1210/er.2017-00211 · Cited by 787 · see citing works
The Role of Lipid Sensing Nuclear Receptors (PPARs and LXR) and Metabolic Lipases in Obesity, Diabetes and NAFLD
Dixon, E. D., Nardo, A. D., Claudel, T., & Trauner, M. (2021) · Genes · doi:10.3390/genes12050645 · Cited by 114 · see citing works
Maternal Obesity during Gestation Impairs Fatty Acid Oxidation and Mitochondrial SIRT3 Expression in Rat Offspring at Weaning
Borengasser, S. J., Lau, F., Kang, P., Blackburn, M. L., Ronis, M. J. J., Badger, T. M., & Shankar, K. (2011) · PLoS ONE · doi:10.1371/journal.pone.0024068 · Cited by 107 · see citing works
Using Metabolomic Profiles as Biomarkers for Insulin Resistance in Childhood Obesity: A Systematic Review
Zhao, X. Y., Gang, X., Liu, Y., Sun, C., Han, Q., & Wang, G. (2016) · Journal of Diabetes Research · doi:10.1155/2016/8160545 · Cited by 70 · see citing works
The relevance of increased fat oxidation for body‐weight management: metabolic inflexibility in the predisposition to weight gain
Astrup, A. V. (2011) · Obesity Reviews · doi:10.1111/j.1467-789x.2011.00894.x · Cited by 66 · see citing works
Adipocyte NR1D1 dictates adipose tissue expansion during obesity
Hunter, L., Pelekanou, C. E., Barron, N. J., Northeast, R. C., Grudzien, M., Adamson, A. D., Downton, P. J., Cornfield, T., Cunningham, P. S., Billaud, J.-N., et al. (2021) · eLife · doi:10.7554/elife.63324 · Cited by 63 · see citing works
Effects of high-intensity interval training on physical capacities and substrate oxidation rate in obese adolescents
Lazzer, S., Tringali, G., Caccavale, M., Micheli, R. D., Abbruzzese, L., & Sartório, A. (2016) · Journal of Endocrinological Investigation · doi:10.1007/s40618-016-0551-4 · Cited by 61 · see citing works
Metabolic Inflexibility as a Pathogenic Basis for Atrial Fibrillation
Qin, X., Zhang, Y., & Zheng, Q. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23158291 · Cited by 38 · see citing works
Autonomic Nervous System and Cardiac Metabolism
Chakraborty, P., Farhat, K., Po, S. S., Armoundas, A. A., & Stavrakis, S. (2023) · JACC. Clinical electrophysiology · doi:10.1016/j.jacep.2023.02.019 · Cited by 29 · see citing works
Effects of Aerobic Exercise on Blood Lipids in People with Overweight or Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Chen, Z., Zhou, R., Liu, X., Wang, J., Wang, L., Lv, Y., & Yu, L. (2025) · Life · doi:10.3390/life15020166 · Cited by 32 · see citing works
Impaired response to exercise intervention in the vasculature in metabolic syndrome
Knaub, L. A., McCune, S. A., Chicco, A. J., Miller, M. W., Moore, R. L., Birdsey, N., Lloyd, M. I., Villarreal, J., Keller, A. C., Watson, P. A., et al. (2012) · Diabetes and Vascular Disease Research · doi:10.1177/1479164112459664 · Cited by 27 · see citing works
Reduced Carbohydrate Diet to Improve Metabolic Outcomes and Decrease Adiposity in Obese Peripubertal African American Girls
Casazza, K., Cardel, M. I., Dulin, A., Hanks, L. J., Gower, B. A., Newton, A. L., & Wallace, S. B. (2011) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/mpg.0b013e31823df207 · Cited by 27 · see citing works
Role of adipose tissue inflammation in fat pad loss induced by fasting in lean and mildly obese mice
Lacerda, D. R., Costa, K. A., Silveira, A. L. M., Rodrigues, D. F., Silva, A. N., Sabino, J. L., Pinho, V., Menezes, G. B., Soares, D. D., Teixeira, M. M., et al. (2019) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2019.06.006 · Cited by 19 · see citing works
Alterations in the carnitine cycle in a mouse model of Rett syndrome
Mucerino, S., Salle, A. D., Alessio, N., Margarucci, S., Nicolai, R., Melone, M. A. B., Galderisi, U., & Peluso, G. (2017) · Scientific Reports · doi:10.1038/srep41824 · Cited by 18 · see citing works
Acute Effect of Fatmax Exercise on the Metabolism in Overweight and Nonoverweight Girls
Zakrzewski-Fruer, J. K., & Tolfrey, K. (2012) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e31825804cf · Cited by 18 · see citing works
miR-183 and miR-96 orchestrate both glucose and fat utilization in skeletal muscle
Wang, H., Ma, M., Li, Y., Liu, J., Sun, C., Liu, S., Yan, Y., Yan, Y., Tang, Z., Shen, S., et al. (2021) · EMBO Reports · doi:10.15252/embr.202052247 · Cited by 16 · see citing works
Mitochondrial Utilization of Competing Fuels Is Altered in Insulin Resistant Skeletal Muscle of Non-obese Rats (Goto-Kakizaki)
Lai, N., Fealy, C. E., Kummitha, C., Cabras, S., Kirwan, J. P., & Hoppel, C. L. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00677 · Cited by 15 · see citing works
A single exercise session increases insulin sensitivity in normal weight and overweight/obese adolescents
Short, K. R., Pratt, L. V., & Teague, A. M. (2018) · Pediatric Diabetes · doi:10.1111/pedi.12684 · Cited by 15 · see citing works
Metabolic Response to Submaximal and Maximal Exercise in People with Severe Obesity, Prediabetes, and Diabetes
Battista, F., Belligoli, A., Neunhäeuserer, D., Gasperetti, A., Bettini, S., Compagnin, C., Marchese, R., Quinto, G., Bergamin, M., Vettor, R., et al. (2021) · Obesity Facts · doi:10.1159/000517589 · Cited by 14 · see citing works
Effects of cardiorespiratory fitness and body mass index on cardiometabolic risk factors in schoolchildren
Bagatini, N. C., Pinho, C. D. F., Leites, G. T., Voser, R. D. C., Gaya, A. R., & Cunha, G. D. S. (2023) · BMC Pediatrics · doi:10.1186/s12887-023-04266-w · Cited by 10 · see citing works
Physical activity, exercise and non-communicable diseases
Archer, E., & Blair, S. N. (2012) · doi:10.24804/ree.14.1 · Cited by 10 · see citing works
The continuum of disrupted metabolic tempo, mitochondrial substrate congestion, and metabolic gridlock toward the development of non-communicable diseases
Tippairote, T., Bjørklund, G., & Yaovapak, A. (2021) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2021.1907299 · Cited by 8 · see citing works
The role of pharmacotherapy in the prevention and treatment of paediatric metabolic syndrome – Implications for long-term health
Sabin, M. A., Magnussen, C. G., Juonala, M., Cowley, M. A., & Hamilton-Shield, J. P. (2011) · Pharmacological Research · doi:10.1016/j.phrs.2011.10.003 · Cited by 7 · see citing works
Hormonal and Metabolic Responses to a Single Bout of Resistance Exercise in Prader-Willi Syndrome
Rubin, D. A., Clark, S. J., Haqq, A. M., Castner, D. M., Ng, J., & Judelson, D. A. (2017) · Hormone Research in Paediatrics · doi:10.1159/000454805 · Cited by 6 · see citing works
No difference in exogenous carbohydrate oxidation during exercise in children with and without impaired glucose tolerance
Chu, L., Morrison, K. M., Riddell, M. C., Raha, S., & Timmons, B. W. (2016) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00419.2016 · Cited by 5 · see citing works
Self-citation
Metabolic inflexibility in youth with obesity: Is it a feature of obesity or distinctive of youth who are metabolically unhealthy?
Gebara, N. Y., Kim, J. Y., Bacha, F. F., Lee, S., & Arslanian, S. A. (2021) · Clinical Obesity · doi:10.1111/cob.12501 · Cited by 4 · see citing works
Metabolic responses to walking in children with Prader‐Willi syndrome on growth hormone replacement therapy
Hyde, A. M., Chavoya, F. A., Silveira, F. V., Beam, W. C., & Rubin, D. A. (2018) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.40509 · Cited by 4 · see citing works
Acute Cardiometabolic and Exercise Responses to Breakfast Omission versus Breakfast Consumption in Adolescent Girls: A Randomised Crossover Trial
Zakrzewski-Fruer, J. K., Morari, V., Champion, R. B., Bailey, D. P., Ferrandino, L., & Jones, R. L. (2023) · Nutrients · doi:10.3390/nu15143210 · Cited by 3 · see citing works
Post-exercise Warm or Cold Water Immersion to Augment the Cardiometabolic Benefits of Exercise Training: A Proof of Concept Trial
Russell, B. M., Chang, C. R., Hill, T., Cotter, J. D., & François, M. E. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.759240 · Cited by 3 · see citing works
Nutritional Considerations for the Overweight Young Athlete
Chu, L., & Timmons, B. W. (2015) · Pediatric Exercise Science · doi:10.1123/pes.2015-0052 · Cited by 3 · see citing works
Self-citation
Using Metabolic Testing to Personalize Behavioral Obesity Treatment
Epstein, L. H., Apolzan, J. W., Moore, M., Neuwald, N. V., & Faith, M. S. (2025) · Obesity Science & Practice · doi:10.1002/osp4.70065 · Cited by 2 · see citing works
Metabolic Flexibility During Exercise in Children with Overweight/Obesity Versus Children who are Lean
Dykstra, B. J., Kuszmaul, D. J., & Mahon, A. D. (2022) · Pediatric Exercise Science · doi:10.1123/pes.2021-0229 · Cited by 2 · see citing works
Severely obese adolescent girls rely earlier on carbohydrates during walking than normal-weight matched girls
Gavarry, O., Aguer, C., Delextrat, A. A., Lentin, G., Ayme, K., & Boussuges, A. (2015) · Journal of Sports Sciences · doi:10.1080/02640414.2015.1021274 · Cited by 2 · see citing works
Assessment of insulin resistance in the skeletal muscle of mice using positron emission tomography/computed tomography imaging
Miyatake, Y., Izumi-Mishima, Y., Tsutsumi, R., Otani, T., Suemasa, N., Masumoto, S., Kuroda, M., & Sakaue, H. (2020) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2020.05.165 · Cited by 2 · see citing works
Lower Plasma Lactate Concentrations After Training Support the Hypothesis of Improved Metabolic Flexibility in Male Long-Term Selected Marathon Mice Compared to Unselected Controls
Brenmoehl, J., Meyer, Z., Walz, C., Ohde, D., & Hoeflich, A. (2024) · Cells · doi:10.3390/cells13242123 · Cited by 1 · see citing works
Metabolic mechanisms of the fat mass and obesity-associated (FTO) gene
Danaher, J. (2016) · Victoria University Research Repository (Victoria University) · Cited by 1 · see citing works
THE ASSOCIATIONS BETWEEN DIET QUALITY, TOTAL AND REGIONAL ADIPOSITY, AND METABOLIC RISK IN HISPANIC AND NON-HISPANIC ADOLESCENT GIRLS
Vassallo, D. M. (2015) · UA Campus Repository (The University of Arizona)
MATERNAL OBESITY AND OXIDATIVE STRESS IN THE FETUS: MECHANISMS UNDERLYING EARLY LIFE SHIFTS IN SKELETAL MUSCLE METABOLISM
Boyle, K. E., & Friedman, J. E. (2011) · Fetal and Maternal Medicine Review · doi:10.1017/s0965539511000118
The Metabolic Effects of Low Grade Inflammation on Postprandial Metabolism Following a High Fat Meal
Pittman, J. T. (2013) · VTechWorks (Virginia Tech)
Metabolic flexibility and obesity in children and youth
Galea, V. (2012) · Yearbook of Sports Medicine · doi:10.1016/j.yspm.2011.08.026
The Relationship Between Diet, Body Composition, Cardiorespiratory Fitness and Respiratory Quotient
Bouchard, I. (2019) · KU ScholarWorks (University of Kansas)
Assessment of Medial Gastrocnemius Thickness and Stiffness in Children with Obesity Using Shear Wave Elastography
Dağ, N., Dündar, İ., Güngör, Ş., Taşolar, S., Ulubaba, H. E., akyol, R., & Güngör, E. D. (2026) · Children · doi:10.3390/children13101320
Effect of manipulations in exercise and breakfast on metabolism in overweight and non-overweight children and adolescents
Zakrzewski-Fruer, J. K. (2012) · Loughborough University Research Repository (Loughborough University)

Metabolic Flexibility during Exercise in Children with Obesity and Matched Controls
Chu, L., Morrison, K. M., Riddell, M. C., Raha, S., & Timmons, B. W. (2020) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000002428 · Cited by 4 · see citing works
Self-citation
Metabolic inflexibility in youth with obesity: Is it a feature of obesity or distinctive of youth who are metabolically unhealthy?
Gebara, N. Y., Kim, J. Y., Bacha, F. F., Lee, S., & Arslanian, S. A. (2021) · Clinical Obesity · doi:10.1111/cob.12501 · Cited by 4 · see citing works
Metabolic flexibility across the spectrum of glycemic regulation in youth
Bacha, F. F., Bartz, S. K., Puyau, M. R., Adolph, A. L., & Sharma, S. (2021) · JCI Insight · doi:10.1172/jci.insight.146000 · Cited by 17 · see citing works
Metabolic Flexibility During Exercise In Overweight/obese Children Vs. Lean Children
Dykstra, B. J., Kuszmaul, D. J., & Mahon, A. D. (2020) · Medicine & Science in Sports & Exercise · doi:10.1249/01.mss.0000687424.71417.c9
Metabolic Flexibility In Lean Children
Dykstra, B. J., Hidde, M. C., Erichsen, J. M., & Mahon, A. D. (2017) · Medicine & Science in Sports & Exercise · doi:10.1249/01.mss.0000518081.80513.00

Authors: Aucouturier, J., Duché, P., & Timmons, B. W.
Affiliations: McMaster University (CA)
Université Blaise Pascal (FR)
Corresponding author: Aucouturier, J.
ORCID: Aucouturier, J.
Duché, P.
Timmons, B. W.
Venue: Obesity Reviews
Publisher: Wiley
Published: 2011-04-27
Volume: 12
Issue: 5
Pages: e44-53
ISSN: 1467-7881 (ISSN-L)
1467-789X
DOI: 10.1111/j.1467-789x.2010.00812.x
OpenAlex: W1568848466
Cited by: 43
References: 62
Citations by year: 2026: 1 · 2025: 2 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 7 · 2020: 2 · 2019: 2 · 2018: 3 · 2017: 2 · 2016: 4 · 2015: 3 · 2013: 1 · 2012: 5
FWCI: 0.50
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Obesity Reviews (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion)
Funders: McMaster University
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords: metabolic flexibility, metabolic inflexibility, childhood obesity, skeletal muscle, substrate oxidation, insulin resistance, type 2 diabetes, nutrient partitioning, energy metabolism, substrate mobilization
MeSH terms: Adipose Tissue, Blood Glucose, Child, Diabetes Mellitus, Type 2, Energy Metabolism, Humans, Obesity, Oxidation-Reduction, Muscle, Skeletal, Adipogenesis

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Metabolic flexibility and obesity in children and youth

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks