Metabolic flexibility
Open accessAbstract
Human physiology needs to be well adapted to cope with major discontinuities in both the supply of and demand for energy. This adaptability requires ‘a clear capacity to utilize lipid and carbohydrate fuels and to transition between them’ ( Kelley et al. 2002 b ). Such capacities characterize the healthy state and can be termed ‘metabolic flexibility’. However, increasing evidence points to metabolic inflexibility as a key dysfunction of the cluster of disease states encompassed by the term ‘metabolic syndrome’. In obese and diabetic individuals this inflexibility is manifest in a range of metabolic pathways and tissues including: (1) failure of cephalic-phase insulin secretion (impaired early-phase prandial insulin secretion concomitant with failure to suppress hepatic glucose production and NEFA efflux from adipose tissue); (2) failure of skeletal muscle to appropriately move between use of lipid in the fasting state and use of carbohydrate in the insulin-stimulated prandial state; (3) impaired transition from fatty acid efflux to storage in response to a meal. Finally, it is increasingly clear that reduced capacity for fuel usage in, for example, skeletal muscle, as indicated by reduced mitochondrial size and density, is characteristic of the metabolic syndrome state and a fundamental component of metabolic inflexibility. Key questions that remain are how metabolic flexibility is lost in obese and diabetic individuals and by what means it may be regained.
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Skeletal muscle oxidative and fat-metabolism defects track closely with insulin sensitivity and are thought to help cause insulin resistance.
“Defects in skeletal muscle oxidative capacity and fat metabolism are highly correlated with insulin sensitivity (IS) (1,5,12) and are believed to contribute to the pathogenesis of insulin resistance (13,14).”
From Dynamic changes in fat oxidation in human primary myocytes mirror metabolic characteristics of the donor (2005) · cites this paper as [13]
In insulin-stimulated states, people with obesity preferentially oxidize fats rather than glucose.
“Consequently, individuals with obesity tend to oxidize lipids instead of metabolizing glucose under insulin-stimulated conditions121.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [121]
Metabolic inflexibility is present in obese people, who oxidize lipids in insulin-stimulated conditions instead of metabolizing glucose, with mitochondria being key organelles affecting this incapacity.
“This impairment is known as 'metabolic inflexibility' (Griffin et al., 2015), that is present in obese people since they are able to oxidize lipids in insulin-stimulated conditions instead to metabolize glucose being mitochondria the key organelles affecting this incapacity (Storlien et al., 2004).”
From Mitochondrial Activity and Dynamics Changes Regarding Metabolism in Ageing and Obesity (2017) · cites this paper as Storlien et al., 2004
Metabolic inflexibility is present in obese people because they oxidize lipids in insulin-stimulated conditions instead of metabolizing glucose.
“that is present in obese people since they are able to oxidize lipids in insulin-stimulated conditions instead to metabolize glucose”
From Mitochondrial Activity and Dynamics Changes Regarding Metabolism in Ageing and Obesity (2017) · cites this paper as Storlien et al., 2004
Mitochondria are the key organelles affecting metabolic inflexibility.
“being mitochondria the key organelles affecting this incapacity (Storlien et al., 2004).”
From Mitochondrial Activity and Dynamics Changes Regarding Metabolism in Ageing and Obesity (2017) · cites this paper as Storlien et al., 2004
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Mootha, V. K., Lindgren, C. M., Eriksson, K.-F., Subramanian, A., Sihag, S., Lehar, J., Puigserver, P., Carlsson, E., Ridderstråle, M., Laurila, E., et al. (2003) · Nature Genetics · doi:10.1038/ng1180 · Cited by 10,197 · see citing works
Wu, Z., Puigserver, P., Andersson, U., Zhang, C., Adelmant, G., Mootha, V., Troy, A., Cinti, S., Lowell, B., Scarpulla, R. C., et al. (1999) · Cell · doi:10.1016/s0092-8674(00)80611-x · Cited by 4,139 · see citing works
Transcriptional co-activator PGC-1α drives the formation of slow-twitch muscle fibres
Lin, J., Wu, H., Tarr, P. T., Zhang, C.-Y., Wu, Z., Boss, O., Michael, L. F., Puigserver, P., Isotani, E., Olson, E. N., et al. (2002) · Nature · doi:10.1038/nature00904 · Cited by 2,546 · see citing works
Dysfunction of Mitochondria in Human Skeletal Muscle in Type 2 Diabetes
Kelley, D. E., He, J., Menshikova, E. V., & Ritov, V. B. (2002) · Diabetes · doi:10.2337/diabetes.51.10.2944 · Cited by 2,321 · see citing works
Self-citationMitochondrial dysfunction in the elderly: possible role in insulin resistance
Petersen, K. F., Befroy, D., Dufour, S., Dziura, J., Ariyan, C., Rothman, D. L., DiPietro, L., Cline, G. W., & Shulman, G. I. (2003) · Science · doi:10.1126/science.1082889 · Cited by 2,107 · see citing works
Patti, M. E., Butte, A. J., Crunkhorn, S., Cusi, K., Berria, R., Kashyap, S., Miyazaki, Y., Kohane, I., Costello, M., Saccone, R., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1032913100 · Cited by 1,952 · see citing works
Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1
Yoon, J. C., Puigserver, P., Chen, G., Donovan, J., Wu, Z., Rhee, J., Adelmant, G., Stafford, J., Kahn, C. R., Granner, D. K., et al. (2001) · Nature · doi:10.1038/35093050 · Cited by 1,821 · see citing works
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
Self-citationFuel 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
Self-citationAdiponectin Expression From Human Adipose Tissue
Kern, P. A., Di Gregorio, G. B., Lu, T., Rassouli, N., & Ranganathan, G. (2003) · Diabetes · doi:10.2337/diabetes.52.7.1779 · Cited by 875 · see citing works
Adipose tissue as a buffer for daily lipid flux
Frayn, K. (2002) · Diabetologia · doi:10.1007/s00125-002-0873-y · Cited by 752 · see citing works
Acquirement of brown fat cell features by human white adipocytes
Tiraby, C., Tavernier, G., Lefort, C., Larrouy, D., Bouillaud, F., Ricquier, D., & Langin, D. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305235200 · Cited by 474 · see citing works
MEF2 responds to multiple calcium‐regulated signals in the control of skeletal muscle fiber type
Wu, H., Naya, F. J., McKinsey, T. A., Mercer, B., Shelton, J. M., Chin, E. R., Simard, A. R., Michel, R. N., Bassel‐Duby, R., Olson, E. N., et al. (2000) · The EMBO Journal · doi:10.1093/emboj/19.9.1963 · Cited by 468 · see citing works
M <scp>USCLE</scp> T <scp>RIGLYCERIDE AND</scp> I <scp>NSULIN</scp> R <scp>ESISTANCE</scp>
Kelley, D. E., Goodpaster, B. H., & Storlien, L. (2002) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.22.010402.102912 · Cited by 364 · see citing works
Self-citationAdipose tissue metabolism in obesity: Lipase action in vivo before and after a mixed meal
Coppack, S. W., Evans, R. D., Fisher, R. M., Frayn, K. N., Gibbons, G. F., Humphreys, S. M., Kirk, M. L., Potts, J. L., & Hockaday, T. D. R. (1992) · Metabolism · doi:10.1016/0026-0495(92)90269-g · Cited by 278 · see citing works
cDNA Cloning and mRNA Analysis of PGC-1 in Epitrochlearis Muscle in Swimming-Exercised Rats
Goto, M., Terada, S., Kato, M., Katoh, M., Yokozeki, T., Tabata, I., & Shimokawa, T. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3134 · Cited by 258 · see citing works
Bruce, D. G., Chisholm, D. J., Storlien, L. H., & Kraegen, E. W. (1988) · Diabetes · doi:10.2337/diab.37.6.736 · Cited by 232 · see citing works
Self-citationPolyzogopoulou, E., Kalfarentzos, F., Vagenakis, A. G., & Alexandrides, T. K. (2003) · Diabetes · doi:10.2337/diabetes.52.5.1098 · Cited by 232 · see citing works
Meirhaeghe, A., Crowley, V., Lenaghan, C., Lelliott, C. J., GREEN, K., Stewart, A., Kevin, H. A. R. T., Schinner, S., Sethi, J. K., Yeo, G. S. H., et al. (2003) · Biochemical Journal · doi:10.1042/bj20030200 · Cited by 210 · see citing works
Summers, L. K. M., Samra, J. S., Humphreys, S. M., Morris, R. J., & Frayn, K. N. (1996) · Clinical Science · doi:10.1042/cs0910679 · Cited by 167 · see citing works
Response of adipose tissue lipoprotein lipase to the cephalic phase of insulin secretion.
Picard, F., Naïmi, N., Richard, D., & Deshaies, Y. (1999) · Diabetes · doi:10.2337/diabetes.48.3.452 · Cited by 83 · see citing works
Plasma Adiponectin Increases Postprandially in Obese, but not in Lean, Subjects
English, P., Coughlin, S. R., Hayden, K., Malik, I. A., & Wilding, J. P. H. (2003) · Obesity Research · doi:10.1038/oby.2003.115 · Cited by 73 · see citing works
Sympathetic control of white adipose tissue in lean and obese humans
Dodt, C., Lönnroth, P., Wellhoner, J. P., Fehm, H. L., & Elam, M. (2003) · Acta Physiologica Scandinavica · doi:10.1046/j.1365-201x.2003.01077.x · Cited by 67 · see citing works
Hypothalamic monoamines associated with the cephalic phase insulin response
Holmes, L. J., Storlien, L. H., & Smythe, G. A. (1989) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1989.256.2.e236 · Cited by 12 · see citing works
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Flagged first, then by citations
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- Kelley DE, Goodpaster BH & Storlien LH (2002a) Muscle triglycerides and insulin resistance. Annual Review of Nutrition 22, 325-346.
Cited by
Sorted by citations
Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC‐1α
Gerhart‐Hines, Z., Rodgers, J. T., Bare, O., Lerin, C., Kim, S., Mostoslavsky, R., Alt, F. W., Wu, Z., & Puigserver, P. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601633 · Cited by 1,294 · see citing works
Disordered lipid metabolism and the pathogenesis of insulin resistance.
Savage, D. B., Petersen, K. F., & Shulman, G. I. (2007) · Physiological Reviews · doi:10.1152/physrev.00024.2006 · Cited by 1,107 · see citing works
Mitochondrial and metabolic dysfunction in ageing and age-related diseases
Amorim, J. A., Coppotelli, G., Rolo, A. P., Palmeira, C. M., Ross, J. M., & Sinclair, D. A. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00626-7 · Cited by 990 · see citing works
Mitochondrial Dynamics in Mammalian Health and Disease
Liesa, M., Palacín, M., & Zorzano, A. (2009) · Physiological Reviews · doi:10.1152/physrev.00030.2008 · Cited by 953 · see citing works
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
Short-term cold acclimation improves insulin sensitivity in patients with type 2 diabetes mellitus
Hanssen, M. J. W., Joris Hoeks, J., Brans, B. T., van der Lans, A. A. J. J., Schaart, G., van den Driessche, J. J., Jörgensen, J. A., Boekschoten, M. V., Hesselink, M. K. C., Havekes, B., et al. (2015) · Nature Medicine · doi:10.1038/nm.3891 · Cited by 587 · see citing works
Bays, H. E., González-Campoy, J. M., Bray, G. A., Kitabchi, A. E., Bergman, D. A., Schorr, A. B., Rodbard, H. W., & Henry, R. R. (2008) · Expert Review of Cardiovascular Therapy · doi:10.1586/14779072.6.3.343 · Cited by 531 · see citing works
Exercise training‐induced improvements in insulin action
Hawley, J. A., & Lessard, S. J. (2008) · Acta Physiologica · doi:10.1111/j.1748-1716.2007.01783.x · Cited by 454 · see citing works
The pivotal role of pyruvate dehydrogenase kinases in metabolic flexibility
Zhang, S., Hulver, M. W., McMillan, R. P., Cline, M. A., & Gilbert, E. R. (2014) · Nutrition & Metabolism · doi:10.1186/1743-7075-11-10 · Cited by 450 · see citing works
Biology's response to dieting: the impetus for weight regain
MacLean, P. S., Bergouignan, A., Cornier, M., & Jackman, M. R. (2011) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00755.2010 · Cited by 449 · see citing works
A lipase-independent pathway of lipid release and immune modulation by adipocytes
Flaherty, S. E., Grijalva, A., Xu, X., Ables, E. V., Nomani, A., & Ferrante, A. W. (2019) · Science · doi:10.1126/science.aaw2586 · Cited by 378 · see citing works
The metabolic syndrome: role of skeletal muscle metabolism.
Stump, C. S., Henriksen, E. J., Wei, Y., & Sowers, J. R. (2006) · Annals of Medicine · doi:10.1080/07853890600888413 · Cited by 362 · see citing works
Phielix, E., Schrauwen-Hinderling, V. B., Mensink, M., Lenaers, E., Meex, R., Hoeks, J., Kooi, M. E., Moonen-Kornips, E., Sels, J.-P., Hesselink, M. K. C., et al. (2008) · Diabetes · doi:10.2337/db08-0391 · Cited by 359 · see citing works
Aging is accompanied by a blunted muscle protein synthetic response to protein ingestion
Wall, B. T., Gorissen, S. H., Pennings, B., Koopman, R., Groen, B. B. L., Verdijk, L. B., & van Loon, L. J. C. (2015) · PLOS ONE · doi:10.1371/journal.pone.0140903 · Cited by 352 · see citing works
Glucose transport and sensing in the maintenance of glucose homeostasis and metabolic harmony
Herman, M. A. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29027 · Cited by 349 · see citing works
Lipid and lipoprotein dysregulation in insulin resistant states
Avramoglu, R. K., Basciano, H., & Adeli, K. (2006) · Clinica Chimica Acta · doi:10.1016/j.cca.2005.12.026 · Cited by 318 · see citing works
Dietary Sugars Stimulate Fatty Acid Synthesis in Adults3
Parks, E. J., Skokan, L. E., Timlin, M. T., & Dingfelder, C. S. (2008) · Journal of Nutrition · doi:10.1093/jn/138.6.1039 · Cited by 315 · see citing works
Skeletal muscle fat oxidation: Timing and flexibility are everything
Kelley, D. E. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25758 · Cited by 298 · see citing works
Self-citationSirt3 regulates metabolic flexibility of skeletal muscle through reversible enzymatic deacetylation
Jing, E., O’Neill, B. T., Rardin, M. J., Kleinridders, A., Ilkeyeva, O. R., Ussar, S., Bain, J. R., Lee, K. Y., Verdin, E. M., Newgard, C. B., et al. (2013) · Diabetes · doi:10.2337/db12-1650 · Cited by 283 · see citing works
Targeting the AMPK pathway for the treatment of Type 2 diabetes
Viollet, B. (2009) · Frontiers in bioscience · doi:10.2741/3460 · Cited by 281 · see citing works
Wells, J. C. K. (2009) · American Journal of Human Biology · doi:10.1002/ajhb.20994 · Cited by 269 · see citing works
San-Millán, I., & Brooks, G. A. (2018) · Sports Medicine · doi:10.1007/s40279-017-0751-x · Cited by 264 · see citing works
NCoR1 Is a Conserved Physiological Modulator of Muscle Mass and Oxidative Function
Yamamoto, H., Williams, E. G., Mouchiroud, L., Cantó, C., Fan, W., Downes, M., Héligon, C., Barish, G. D., Desvergne, B., Evans, R. M., et al. (2011) · Cell · doi:10.1016/j.cell.2011.10.017 · Cited by 261 · see citing works
Anticipatory physiological regulation in feeding biology: Cephalic phase responses
Power, M. L., & Schulkin, J. (2008) · Appetite · doi:10.1016/j.appet.2007.10.006 · Cited by 258 · see citing works
Skeletal muscle mitochondria as a target to prevent or treat type 2 diabetes mellitus
Hesselink, M. K. C., Schrauwen-Hinderling, V., & Schrauwen, P. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.104 · Cited by 242 · see citing works
"Sick fat," metabolic disease, and atherosclerosis.
Bays, H. (2009) · American Journal of Medicine · doi:10.1016/j.amjmed.2008.10.015 · Cited by 252 · see citing works
Fatty acid metabolism is enhanced in type 2 diabetic hearts
Carley, A. N., & Severson, D. L. (2005) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2005.03.005 · Cited by 232 · see citing works
Chibalin, A. V., Leng, Y., Vieira, E., Krook, A., Björnholm, M., Long, Y. C., Kotova, O., Zhong, Z., Sakane, F., Steiler, T., et al. (2008) · Cell · doi:10.1016/j.cell.2007.12.035 · Cited by 232 · see citing works
Ukropcova, B., McNeil, M., Sereda, O., de Jonge, L., Xie, H., Bray, G. A., & Smith, S. R. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24332 · Cited by 213 · see citing works
Role of mitochondrial dynamics proteins in the pathophysiology of obesity and type 2 diabetes
Zorzano, A., Liesa, M., & Palacín, M. (2009) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2009.02.004 · Cited by 209 · see citing works
Interorgan Metabolic Crosstalk in Human Insulin Resistance
Gancheva, S., Jeleník, T., Álvarez-Hernández, E., & Roden, M. (2018) · Physiological Reviews · doi:10.1152/physrev.00015.2017 · Cited by 192 · see citing works
Richards, J. C., Johnson, T. K., Kuzma, J. N., Lonac, M. C., Schweder, M. M., Voyles, W. F., & Bell, C. (2010) · The Journal of Physiology · doi:10.1113/jphysiol.2010.189886 · Cited by 187 · see citing works
Vroegrijk, I. O. C. M., van Diepen, J. A., van den Berg, S. A. A., Westbroek, I., Keizer, H. G., Gambelli, L., Hontecillas, R., Bassaganya-Riera, J., Zondag, G. C. M., Romijn, J. A., et al. (2011) · Food and Chemical Toxicology · doi:10.1016/j.fct.2011.03.037 · Cited by 177 · see citing works
Differential role of insulin/IGF-1 receptor signaling in muscle growth and glucose homeostasis
O’Neill, B. T., Lauritzen, H. P. M. M., Hirshman, M. F., Smyth, G., Goodyear, L. J., & Kahn, C. R. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.04.037 · Cited by 173 · see citing works
Ukropcova, B., Sereda, O., de Jonge, L., Bogacka, I., Nguyen, T., Xie, H., Bray, G. A., & Smith, S. R. (2007) · Diabetes · doi:10.2337/db06-0521 · Cited by 165 · see citing works
Mitochondrial response to nutrient availability and its role in metabolic disease
Gao, A. W., Cantó, C., & Houtkooper, R. H. (2014) · EMBO Molecular Medicine · doi:10.1002/emmm.201303782 · Cited by 148 · see citing works
Huang, J., Jones, D., Luo, B., Sanderson, M. J., Soto, J. E., Abel, E. D., Cooksey, R. C., & McClain, D. A. (2010) · Diabetes · doi:10.2337/db10-0593 · Cited by 146 · see citing works
Scherer, P. E. (2016) · Diabetes · doi:10.2337/db16-0339 · Cited by 133 · see citing works
“We know that the systemic ability to adjust to changing nutrient conditions—a phenomenon that we refer to as metabolic flexibility (5)—very much depends on the ability of the adipocyte and adipose tissue to expand”
How neural mediation of anticipatory and compensatory insulin release helps us tolerate food
Teff, K. L. (2011) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.01.012 · Cited by 126 · see citing works
Mitochondrial dynamics as a bridge between mitochondrial dysfunction and insulin resistance
Zorzano, A., Liesa, M., & Palacı́n, M. (2009) · Archives of Physiology and Biochemistry · doi:10.1080/13813450802676335 · Cited by 123 · see citing works
Nahlé, Z., Hsieh, M., Pietka, T., Coburn, C. T., Grimaldi, P. A., Zhang, M. Q., Das, D., & Abumrad, N. A. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m706478200 · Cited by 122 · see citing works
Miljkovic-Gacic, I., Gordon, C. L., Goodpaster, B. H., Bunker, C. H., Patrick, A. L., Kuller, L. H., Wheeler, V. W., Evans, R. W., & Zmuda, J. M. (2008) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/87.6.1590 · Cited by 122 · see citing works
Hughes, R. L., Kable, M. E., Marco, M., & Keim, N. L. (2019) · Advances in Nutrition · doi:10.1093/advances/nmz049 · Cited by 117 · see citing works
Croci, I., Byrne, N. M., Choquette, S., Hills, A. P., Chachay, V., Clouston, A. D., O'Moore‐Sullivan, T. M., Macdonald, G. A., Prins, J. B., & Hickman, I. J. (2012) · Gut · doi:10.1136/gutjnl-2012-302789 · Cited by 114 · see citing works
Inflammaging, hormesis and the rationale for anti-aging strategies
Santoro, A., Martucci, M., Conte, M., Capri, M., Franceschi, C., & Salvioli, S. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101142 · Cited by 114 · see citing works
Is adiposopathy (sick fat) an endocrine disease?
Bays, H., González-Campoy, J., Henry, R., Bergman, D., Kitabchi, A., Schorr, A., & Rodbard, H. (2008) · International journal of clinical practice · doi:10.1111/j.1742-1241.2008.01848.x · Cited by 121 · see citing works
Oxidative stress, aging, antioxidant supplementation and their impact on human health: An overview
Martemucci, G., Portincasa, P., Ciaula, A. D., Mariano, M., Centonze, V., & D‘Alessandro, A. G. (2022) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2022.111707 · Cited by 110 · see citing works
Flachs, P., Rühl, R., Hensler, M., Janovská, P., Zouhar, P., Kůs, V., Jílková, Z. M., Papp, E., Kuda, O., Svobodová, M., et al. (2011) · Diabetologia · doi:10.1007/s00125-011-2233-2 · Cited by 109 · see citing works
Regulation of the PDK4 Isozyme by the Rb-E2F1 Complex
Hsieh, M., Das, D., Sambandam, N., Zhang, M. Q., & Nahle, Z. A. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m802418200 · Cited by 108 · see citing works
Mitochondrial Activity and Dynamics Changes Regarding Metabolism in Ageing and Obesity
López-Lluch, G. (2017) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2016.12.005 · Cited by 103 · see citing works
“This impairment is known as “metabolic inflexibility” (Griffin et al., 2015), that is present in obese people since they are able to oxidize lipids in insulin-stimulated conditions instead to metabolize glucose being mitochondria the key organelles affecting this incapacity (Storlien et al., 2004).”
BackgroundImproved insulin sensitivity and metabolic flexibility in ghrelin receptor knockout mice.
Longo, K., Charoenthongtrakul, S., Giuliana, D. J., Govek, E., McDonagh, T., Qi, Y., Distefano, P., & Geddes, B. (2008) · Regulatory Peptides · doi:10.1016/j.regpep.2008.03.011 · Cited by 105 · see citing works
The risks of sarcopenia, falls and fractures in patients with type 2 diabetes mellitus
Sarodnik, C., Bours, S., Schaper, N. C., van den Bergh, J. P., & van Geel, T. A. C. M. (2017) · Maturitas · doi:10.1016/j.maturitas.2017.12.011 · Cited by 100 · see citing works
Calçada, D., Vianello, D., Giampieri, E., Sala, C., Castellani, G., de Graaf, A., Kremer, B., van Ommen, B., Feskens, E., Santoro, A., et al. (2014) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2014.01.004 · Cited by 97 · see citing works
ESTERLINE, R. L., Vaag, A. A., Oscarsson, J., & Vora, J. P. (2018) · European Journal of Endocrinology · doi:10.1530/eje-17-0832 · Cited by 97 · see citing works
Basciano, H., Miller, A., Naples, M., Baker, C., Kohen, R., Xu, E., Su, Q., Allister, E. M., Wheeler, M. B., & Adeli, K. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90764.2008 · Cited by 97 · see citing works
Metabolic insight into mechanisms of high-altitude adaptation in Tibetans
Ge, R.-L., Simonson, T. S., Cooksey, R. C., Tanna, U., Ga, Q., Huff, C. D., Witherspoon, D. J., Xing, J., Zhengzhong, B., Prchal, J. T., et al. (2012) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2012.03.003 · Cited by 96 · see citing works
Kulkarni, S. S., Salehzadeh, F., Fritz, T., Zierath, J. R., Krook, A., & Osler, M. E. (2011) · Metabolism · doi:10.1016/j.metabol.2011.06.014 · Cited by 94 · see citing works
Nguyen, D. J. M., Jean, W. H., Jahoor, F., & Rajagopal, V. S. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-2376 · Cited by 93 · see citing works
Ide, T., Brown‐Endres, L., Chu, K., Ongusaha, P. P., Ohtsuka, T., El‐Deiry, W. S., Aaronson, S. A., & Lee, S. W. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.09.031 · Cited by 92 · see citing works
RetractedCholesterol homeostasis: Researching a dialogue between the brain and peripheral tissues
Gliozzi, M., Musolino, V., Bosco, F., Scicchitano, M., Scarano, F., Nucera, S., Zito, M. C., Ruga, S., Carresi, C., Macrì, R., et al. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.105215 · Cited by 92 · see citing works
Baskin, K. K., Grueter, C. E., Kusminski, C. M., Holland, W. L., Bookout, A. L., Satapati, S., Kong, Y. M., Burgess, S. C., Malloy, C. R., Scherer, P. E., et al. (2014) · EMBO Molecular Medicine · doi:10.15252/emmm.201404218 · Cited by 90 · see citing works
Tan, G. D., Neville, M. J., Liverani, E., Humphreys, S. M., Currie, J. M., Dennis, L., Fielding, B. A., & Karpe, F. (2005) · Diabetologia · doi:10.1007/s00125-005-0044-z · Cited by 84 · see citing works
Devries, M. C., Samjoo, I. A., Hamadeh, M. J., McCready, C., Raha, S., Watt, M. J., Steinberg, G. R., & Tarnopolsky, M. A. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-2044 · Cited by 82 · see citing works
Fentz, J., Kjøbsted, R., Birk, J. B., Jordy, A. B., Jeppesen, J. F., Thorsen, K., Schjerling, P., Kiens, B., Jessen, N., Viollet, B., et al. (2015) · The FASEB Journal · doi:10.1096/fj.14-266650 · Cited by 82 · see citing works
Obesity and energy balance: is the tail wagging the dog?
Wells, J. C. K., & Siervo, M. (2011) · European Journal of Clinical Nutrition · doi:10.1038/ejcn.2011.132 · Cited by 82 · see citing works
Low Physical Activity and Obesity
Telford, R. D. (2007) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e31806215b7 · Cited by 82 · see citing works
Mitochondrial Dysfunction in Age‐Related Metabolic Disorders
Natarajan, V., Chawla, R., Mah, T. K. L., Vivekanandan, R., Tan, S., Sato, P. Y., & Mallilankaraman, K. B. (2020) · PROTEOMICS · doi:10.1002/pmic.201800404 · Cited by 81 · see citing works
Li, Y., Vaitheesvaran, B., Hartil, K., Robinson, A. J., Hoopmann, M. R., Eng, J. K., Kurland, I. J., & Bruce, J. E. (2011) · Journal of Proteome Research · doi:10.1021/pr200313x · Cited by 80 · see citing works
Fat storage and the biology of energy expenditure
Redinger, R. N. (2009) · Translational research · doi:10.1016/j.trsl.2009.05.003 · Cited by 80 · see citing works
Metabolic aspects of high‐altitude adaptation in Tibetans
Ge, R., Simonson, T. S., Gordeuk, V. R., Prchal, J. T., & McClain, D. A. (2015) · Experimental Physiology · doi:10.1113/ep085292 · Cited by 78 · see citing works
Use of dicarboxylic acids in type 2 diabetes
Mingrone, G., Castagneto‐Gissey, L., & Macé, K. (2012) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2012.04177.x · Cited by 78 · see citing works
Regular exercise attenuates the metabolic drive to regain weight after long-term weight loss
MacLean, P. S., HIGGINS, J. A., Wyatt, H. R., Melanson, E. L., Johnson, G. C., Jackman, M. R., Giles, E. D., Brown, I. E., & Hill, J. O. (2009) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00192.2009 · Cited by 78 · see citing works
Amrit, F. R. G., Steenkiste, E. M., Ratnappan, R., Chen, S.-W., McClendon, T. B., Kostka, D., Yanowitz, J. L., Olsen, C. P., & Ghazi, A. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1005788 · Cited by 78 · see citing works
Metabolic Flexibility and Its Impact on Health Outcomes
Palmer, B. F., & Clegg, D. J. (2022) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2022.01.012 · Cited by 77 · see citing works
The Structural and Functional Coordination of Glycolytic Enzymes in Muscle: Evidence of a Metabolon?
Menard, L. M., Maughan, D. W., & Vigoreaux, J. O. (2014) · Biology · doi:10.3390/biology3030623 · Cited by 77 · see citing works
What is “Hyper” in the ALS Hypermetabolism?
Ferri, A., & Coccurello, R. (2017) · Mediators of Inflammation · doi:10.1155/2017/7821672 · Cited by 77 · see citing works
Nunn, A. V. W., Bell, J. D., & Guy, G. W. (2009) · Nutrition & Metabolism · doi:10.1186/1743-7075-6-16 · Cited by 75 · see citing works
The sedentary (r)evolution: Have we lost our metabolic flexibility?
Freese, J., Klement, R. J., Ruiz-Núñez, B., Schwarz, S., & Lötzerich, H. (2017) · F1000Research · doi:10.12688/f1000research.12724.2 · Cited by 74 · see citing works
Changes in fat oxidation in response to various regimes of high intensity interval training (HIIT)
Astorino, T. A., & Schubert, M. M. (2017) · European Journal of Applied Physiology · doi:10.1007/s00421-017-3756-0 · Cited by 74 · see citing works
Samms, R. J., Cheng, C. C., Kharitonenkov, A., Gimeno, R. E., & Adams, A. C. (2016) · Endocrinology · doi:10.1210/en.2015-1722 · Cited by 73 · see citing works
Osler, M. E., & Zierath, J. R. (2007) · Endocrinology · doi:10.1210/en.2007-1441 · Cited by 71 · see citing works
Mingrone, G., Manco, M., Calvani, M., Castagneto, M., Naon, D., & Zorzano, A. (2005) · Diabetologia · doi:10.1007/s00125-005-1918-9 · Cited by 68 · see citing works
Bays, H. (2010) · Expert Review of Cardiovascular Therapy · doi:10.1586/erc.10.125 · Cited by 66 · see citing works
Zorzano, A., Hernández‐Álvarez, M. I., Palacı́n, M., & Mingrone, G. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.02.017 · Cited by 66 · see citing works
Factors affecting human colostrum fatty acid profile: A case study
Sinanoglou, V. J., Cavouras, D., Boutsikou, Τ., Briana, D. D., Lantzouraki, D. Z., Paliatsiou, S., Volaki, P., Bratakos, S., Malamitsi‐Puchner, A., & Zoumpoulakis, P. G. (2017) · PLoS ONE · doi:10.1371/journal.pone.0175817 · Cited by 65 · see citing works
AMPK activators – potential therapeutics for metabolic and other diseases
Zhou, G., Sebhat, I. K., & Zhang, B. B. (2009) · Acta Physiologica · doi:10.1111/j.1748-1716.2009.01967.x · Cited by 63 · see citing works
Wijngaarden, M. A., van der Zon, G. C., van Dijk, K. W., Pijl, H., & Guigas, B. (2013) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00008.2013 · Cited by 63 · see citing works
Glucose-Fatty Acid Interaction in Skeletal Muscle and Adipose Tissue in Insulin Resistance
Cahová, M., Vavřínková, H., & Kazdová, L. (2007) · Physiological Research · doi:10.33549/physiolres.930882 · Cited by 63 · see citing works
Shi, W., Hegeman, M. A., van Dartel, D. A. M., Tang, J., Suarez, M., Swarts, H., van der Hee, B., Arola, L., & Keijer, J. (2017) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201600878 · Cited by 62 · see citing works
Role of Fatty Acids β-Oxidation in the Metabolic Interactions Between Organs
Panov, A. V., Mayorov, V., & Dikalov, S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252312740 · Cited by 63 · see citing works
Giles, E. D., Wellberg, E. A., Astling, D. P., Anderson, S. M., Thor, A. D., Jindal, S., Tan, A. C., Schedin, P. S., & MacLean, P. S. (2012) · Cancer Research · doi:10.1158/0008-5472.can-12-1653 · Cited by 62 · see citing works
Relation of adipose tissue to metabolic flexibility
Sparks, L. M., Ukropcová, B., Smith, J. M., Pasarica, M., Hymel, D., Xie, H., Bray, G. A., Miles, J. M., & Smith, S. R. (2008) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2008.09.052 · Cited by 61 · see citing works
Mitochondrial dysfunction in metabolism and ageing: shared mechanisms and outcomes?
López‐Lluch, G., Hernández‐Camacho, J. D., Fernández‐Ayala, D. J. M., & Navas, P. (2018) · Biogerontology · doi:10.1007/s10522-018-9768-2 · Cited by 57 · see citing works
Tiraby, C., Tavernier, G., Capel, F., Mairal, A., Crampes, F., RAMI, J., Pujol, C., Boutin, J. A., & Langin, D. (2007) · Diabetologia · doi:10.1007/s00125-007-0765-2 · Cited by 56 · see citing works
Wahlig, J. L., Bales, E. S., Jackman, M. R., Johnson, G. C., McManaman, J. L., & MacLean, P. S. (2011) · Obesity · doi:10.1038/oby.2011.196 · Cited by 55 · see citing works
Rogowski, M. P., Flowers, M. T., Stamatikos, A., Ntambi, J. M., & Paton, C. M. (2013) · Journal of Lipid Research · doi:10.1194/jlr.m035865 · Cited by 55 · see citing works
Cubillos, L. X. M., Tulipani, S., Garcia‐Aloy, M., Bulló, M., Tinahones, F. J., & Andrés‐Lacueva, C. (2015) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201500549 · Cited by 53 · see citing works
Mather, K. J., Hutchins, G. D., Perry, K. M., Territo, W. L., Chisholm, R., Acton, A. J., Glick‐Wilson, B. E., Considine, R. V., Moberly, S. P., & DeGrado, T. R. (2016) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00437.2015 · Cited by 53 · see citing works
Ma, S., Huang, Q., Tominaga, T., Liu, C., & Suzuki, K. (2018) · Nutrients · doi:10.3390/nu10111696 · Cited by 53 · see citing works
Færch, K., & Vaag, A. (2011) · Acta Diabetologica · doi:10.1007/s00592-010-0245-x · Cited by 52 · see citing works
- Authors
- Storlien, L., Oakes, N. D., & Kelley, D. E.
- Affiliations
- AstraZeneca (Sweden) (SE)
- University of Pittsburgh (US)
- Corresponding author
- Storlien, Len
- ORCID
- Kelley, David E.
- Venue
- Proceedings of the Nutrition Society
- Publisher
- Cambridge University Press (CUP)
- Published
- 2004-05
- Volume
- 63
- Issue
- 2
- Pages
- 363-368
- ISSN
- 0029-6651 (ISSN-L)
- 1475-2719
- OpenAlex
- W4253185896
- Cited by
- 291
- References
- 24
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 9 · 2023: 6 · 2022: 20 · 2021: 13 · 2020: 10 · 2019: 16 · 2018: 11 · 2017: 15 · 2016: 16 · 2015: 19 · 2014: 18 · 2013: 17 · 2012: 12
- FWCI
- 6.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of The Nutrition Society (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- metabolic flexibility, metabolic inflexibility, metabolic syndrome, obesity, diabetes mellitus, insulin secretion, hepatic glucose production, mitochondrial density, energy homeostasis
- MeSH terms
- Adipose Tissue, Energy Metabolism, Glucose, Humans, Muscle, Skeletal, Metabolic Syndrome
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