The DOI matches its Crossref record; 112 of the 112 references it cites were found in a registry or an index.
Metabolic flexibility in the development of insulin resistance and type 2 diabetes: effects of lifestyle
Abstract
Summary: Lipotoxicity in skeletal muscle plays a critical role in the aetiology of insulin resistance and type 2 diabetes mellitus by interference of lipid metabolites with insulin signalling and action. The dynamics of lipid oxidation and fine tuning with fatty acid uptake and intramyocellular triacylglycerol turnover may be very important to limit the accumulation of lipid intermediates. The use of metabolic inflexibility, defined as the impaired capacity to increase fat oxidation upon increased fatty acid availability and to switch between fat and glucose as the primary fuel source after a meal, does more justice to the complexity of changes in fuel oxidation during the day. Fatty acid availability, uptake and oxidation all play a role in metabolic flexibility and insulin resistance. During high fatty acid availability, fatty acid transporters may limit cellular and mitochondrial fatty acid uptake and thus limit fat oxidation. After a meal, when the demand for fatty acids as fuel is low, an increased fractional extraction of lipids from plasma may promote intramyocellular lipid accumulation and insulin resistance. Furthermore, defects in fuel switching cluster together with impaired mitochondrial content and/or function. Lifestyle changes in dietary fat intake, physical activity and weight loss may improve metabolic flexibility in skeletal muscle, and thereby contribute to the prevention of type 2 diabetes.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“they affect the supply and demand aspects of metabolism, respectively, and have been shown to influence IMCL levels in both aging and obesity [59, 97, 99, 101, 102].”
From Targeting Intramyocellular Lipids to Improve Aging Muscle Function (2025) · cites this paper as [102]
In the citing paper
“In the obese, insulin resistant, and T2DM individuals, the beneficial effects of weight loss on postprandial glycemia and IR are mostly due to the decreased blood levels of NEFA [110,111] and to an improvement in the insulin-mediated suppression of fat oxidation [112].”
From Effects of diet, lifestyle, Chrononutrition and alternative dietary interventions on postprandial Glycemia and insulin resistance (2022) · cites this paper as [111]
In the citing paper
“It has been shown that weight loss alone is effective in improving insulin sensitivity, but it is more likely to improve fasting fat oxidation and mitochondrial function if combined with exercise training [111].”
From Effects of diet, lifestyle, Chrononutrition and alternative dietary interventions on postprandial Glycemia and insulin resistance (2022) · cites this paper as [111]
In the citing paper
“Interestingly, metabolic inflexibility can already be observed in pre-diabetic individuals suffering from insulin resistance (Corpeleijn et al, 2009), limiting the ability to switch from fatty acid breakdown to fat storage after a meal and vice versa (Kelley, 2005).”
From Mitochondrial response to nutrient availability and its role in metabolic disease (2014) · cites this paper as Corpeleijn et al, 2009
In the citing paper
“but lipid accumulation in non-adipose tissues is also highly associated with insulin resistance (Canto & Auwerx, 2009; Corpeleijn et al, 2009; Schooneman et al, 2013).”
From Mitochondrial response to nutrient availability and its role in metabolic disease (2014) · cites this paper as Corpeleijn et al, 2009
Citations
Cites
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
Mechanisms linking obesity to insulin resistance and type 2 diabetes
Kahn, S. E., Hull, R. L., & Utzschneider, K. M. (2006) · Nature · doi:10.1038/nature05482 · Cited by 5,448
Randle, P. J., Garland, P. B., Hales, C. N., & Newsholme, E. A. (1963) · The Lancet · doi:10.1016/s0140-6736(63)91500-9 · Cited by 5,093
Impaired Mitochondrial Activity in the Insulin-Resistant Offspring of Patients with Type 2 Diabetes
Petersen, K. F., Dufour, S., Befroy, D., Garcia, R., & Shulman, G. I. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa031314 · Cited by 2,193
Mitochondrial dysfunction and type 2 diabetes
Lowell, B. B., & Shulman, G. I. (2005) · Science · doi:10.1126/science.1104343 · Cited by 2,070
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
DeFronzo, R. A., Jacot, E., Jequier, E., Maeder, E., Wahren, J., & Felber, J. P. (1981) · Diabetes · doi:10.2337/diab.30.12.1000 · Cited by 1,770
McGarry, J. D. (2002) · Diabetes · doi:10.2337/diabetes.51.1.7 · Cited by 1,435
Itani, S. I., Ruderman, N. B., Schmieder, F., & Boden, G. (2002) · Diabetes · doi:10.2337/diabetes.51.7.2005 · Cited by 1,390
Dresner, A., Laurent, D., Marcucci, M., Griffin, M. E., Dufour, S., Cline, G. W., Slezak, L. A., Andersen, D. K., Hundal, R. S., Rothman, D. L., et al. (1999) · Journal of Clinical Investigation · doi:10.1172/jci5001 · Cited by 1,311
Cited by
Sorted by citations
Items 201–278 of 278
Li, P., Ji, B., Lappa, D., Meijnikman, A. S., Olsson, L. M., Aydin, Ö., Bruin, S. C., van de Laar, A. W. J. M., Tremaroli, V., Luo, H., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.04.26.489057 · Cited by 3
Huang, W., Ruan, W., Huo, C., Lin, Y., Wang, T., Dai, X., Zhai, H., Ma, J., Zhang, J., Jin, L., et al. (2023) · Frontiers in Nutrition · doi:10.3389/fnut.2022.1065188 · Cited by 3
Microbiome-Targeted Therapies: Enhancing Resilience in Metabolic Disorders
Janiad, S., & Rehman, K. (2024) · Springer eBooks · doi:10.1007/978-981-97-3790-1_13 · Cited by 1
Sarić, M. M., Šikić, N. L., Sorić, T., Sarić, A., Ivanišin, A., Brodić, I., & Milić, M. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27125495 · Cited by 2
Metabolic and neural responses to ultraprocessed foods: a randomized, controlled, crossover study
Hutelin, Z., Ahrens, M., Baugh, M. E., Nartey, E., Herald, D. L., Hanlon, A. L., & DiFeliceantonio, A. G. (2026) · Nature Metabolism · doi:10.1038/s42255-026-01619-4
Introductory Chapter: Therapies Based on Kidney Essence and Qi in Chinese Medicine
Li, X.-T. (2017) · InTech eBooks · doi:10.5772/67292
Galactooligosaccharides and substrate and energy metabolism, dietary intake and body composition
Dijck, V. M. A. J. (2016) · MaRBLe · doi:10.26481/marble.2015.v6.382
Assessing metabolic flexibility response to a multifibre diet: a randomised‐controlled trial
Aubin, A., Hornero‐Ramirez, H., Ranaivo, H., Simon, C., Berghe, L. V. D., Favier, N. F., Dussous, I., Roger, L., Laville, M., Béra‐Maillet, C., et al. (2024) · Journal of Human Nutrition and Dietetics · doi:10.1111/jhn.13350 · Cited by 1
Insulin Resistance and Fatty Acid Trafficking
Denton, N., & Karpe, F. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.90371-4 · Cited by 1
Cantó, C. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-811752-1.00017-1 · Cited by 1
Function and dysfunction of fatty acid mobilization: a review.
Beard, J. K., & Yates, D. T. (2019) · Diabesity · doi:10.15562/diabesity.2019.53 · Cited by 1
Alkahtani, S. A. (2012) · Cited by 1
Making lifestyle work : long-term effects in the prevention of type 2 diabetes
Roumen, C. (2009) · Research Publications (Maastricht University) · doi:10.26481/dis.20091106cr · Cited by 1
Levine, T. B., & Levine, A. B. (2012) · Wiley eBooks · doi:10.1002/9781118480045.ch12 · Cited by 1
Studies of the interaction between diabetes family history, exercise, adiposity and metabolic health
Barwell, N. D. (2010) · Enlighten: Theses (The University of Glasgow) · Cited by 1
Commentary: Does Hunger Manipulate Glucose Levels, or Do Glucose Levels Make You Eat?
Corpeleijn, E. (2016) · Journal of the Association for Consumer Research · doi:10.1086/684460 · Cited by 1
Self-citationPohlmeier, A. M. (2013) · ThinkTech (Texas Tech University) · Cited by 1
Hutelin, Z., Ahrens, M., Baugh, M. E., Nartey, E., Herald, D. L., Hanlon, A. L., & DiFeliceantonio, A. G. (2026) · medRxiv · doi:10.64898/2026.04.10.26350599 · Cited by 1
Aye, M. M. (2013) · Repository@Hull (Worktribe) (University of Hull) · Cited by 1
van de Weijer, T. (2013) · Research Publications (Maastricht University) · doi:10.26481/dis.20130705tw
Reinbeck, A. L. (2013) · Univ. Duesseldorf: Duesseldorfer Dokumenten- und Publikationsserver
Fatty acid metabolism in the metabolic syndrome : effects of dietary fat quantity and quality
van Hees, A. M. J. (2011) · Research Publications (Maastricht University) · doi:10.26481/dis.20111111ah
The role of steroid hormones in skeletal muscle metabolism
Salehzadeh, F. (2011) · Figshare
Skeletal muscle fatty acid handling in insulin resistance : the effect of dietary fatty acids
Jans, A. (2012) · Research Publications (Maastricht University) · doi:10.26481/dis.20120427aj
Impaired skeletal muscle fat oxidation as a mechanism for insulin resistance in South Asians
Hall, L. M. L. (2011) · Enlighten: Theses (The University of Glasgow)
Mashili, F. L. (2012) · Figshare
Novel Noninvasive Breath Test Method for Screening Individuals at Risk for Diabetes
Dillon, E. L., & Sheffield‐Moore, M. (2009) · Diabetes Care · doi:10.2337/dc09-0804
Pedersen, B. K., Krogh‐Madsen, R., Thomsen, C. E., Knudsen, S. H., Hansen, L. S., Pedersen, M., Laye, M. J., Kirwan, J. P., Solomon, T. P. J., Malin, S. K., et al. (2015)
Ribeiro, R. J. T. (2010) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT)
The Metabolic Effects of Low Grade Inflammation on Postprandial Metabolism Following a High Fat Meal
Pittman, J. T. (2013) · VTechWorks (Virginia Tech)
Do Probiotics Protect Against the Deleterious Effects of a High-Fat Diet?
Fundaro, G. (2014) · VTechWorks (Virginia Tech)
Li, Q. (2011) · University of Groningen research database (University of Groningen / Centre for Information Technology)
Effekter og metabolisme av ulike fettsyrer i humane skjelettmuskelceller i kultur
Lauvhaug, L. (2011) · NORA - Norwegian Open Research Archives
IJzerman, T. H. (2016) · Research Publications (Maastricht University) · doi:10.26481/dis.20160205ti
Krogh‐Madsen, R., Thomsen, C. E., Solomon, T. P. J., Klarlund, B., Knudsen, S. H., Hansen, L. S., Pedersen, M., & Dejgaard, T. F. (2012)
Dietary polyphenols: modulators of energy and substrate metabolism in obese humans
Most, J. (2016) · Research Publications (Maastricht University) · doi:10.26481/dis.20160115jm
Obesity and the Risk for Type 2 Diabetes
Bray, G. A. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-802928-2.00030-8
Perioperative physiology and optimalisation in bariatric and metabolic surgery
Pouwels (2017) · Research Publications (Maastricht University) · doi:10.26481/dis.20170531sp
Hunschede, S. (2013) · TSpace (University of Toronto)
Endocrine regulation of lipid mobilization in human obesity
Verboven (2017) · Research Publications (Maastricht University) · doi:10.26481/dis.20170703kv
Davis, G. R. (2013) · Louisiana State University · doi:10.31390/gradschool_dissertations.460
Examination of metabolism in diabetic offspring
Russell, R. (2011) · Louisiana State University · doi:10.31390/gradschool_dissertations.1588
The Immediate and Extended Effect of Diet and Exercise on Metabolic Flexibility
Allerton, T. D. (2017) · Louisiana State University · doi:10.31390/gradschool_dissertations.4493
Skeletal Muscle Mitochondrial, Obesity, and High-Fat Feeding
Guillet, C. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-810422-4.00009-9
Cellular functional roles of celastrol on mitochondrial dysfunction-induced insulin resistance
Bakar, A., & Bakar, M. H. A. (2015)
An exploration into the proteins that regulate skeletal muscle lipid metabolism
Whytock, K. L. (2021) · Liverpool John Moores University · doi:10.24377/ljmu.t.00009962
Modelling molecular processes in weight loss
Tareen, S. H. K. (2020) · doi:10.26481/dis.20200325st
Vitamin D in insulin sensitivity and obesity
Pramono, A. (2020) · Research Publications (Maastricht University) · doi:10.26481/dis.20200828ap
The Relationship Between Diet, Body Composition, Cardiorespiratory Fitness and Respiratory Quotient
Bouchard, I. (2019) · KU ScholarWorks (University of Kansas)
Short-chain fatty acids: role in metabolic disorders
Fadieienko, G. D., & Gridnyev, O. (2021) · Modern Gastroenterology · doi:10.30978/mg-2021-2-55
Cabbia, A., Hilbers, P. A. J., & van Riel, N. A. W. (2021) · Metabolites · doi:10.3390/metabo11100695
Skeletal muscle metabolic flexibility: contribution of genetics and lifestyle
Rivas, D. A. (2011) · RMIT Research Repository (RMIT University Library) · doi:10.25439/rmt.27340623
Modulation of fat oxidation: nutritional and pharmacological approach
van Can, J. G. P. (2012) · Research Publications (Maastricht University) · doi:10.26481/dis.20121031jc
Dietary strategies to modulate the metabolic profile and substrate partitioning
Munsters, M. J. M. (2014) · Research Publications (Maastricht University) · doi:10.26481/dis.20140417mm
Impact of gut-derived metabollites on substrate metabolism and metabolic health
Gonzalez Hernandez Manuel, A. (2020) · Research Publications (Maastricht University) · doi:10.26481/dis.20201027mgh
Hüsamettin, K. A. Y. A., & Özdenk, Ç. (2022) · Anatolia Sport Research · doi:10.29228/anatoliasr.28
Moderating carbohydrate digestion rate promotes metabolic flexibility in micePreprint
Hayes, A., Swackhamer, C., Quezada‐Calvillo, R., Butte, N. F., Sterchi, E. E., Nichols, B. L., & Hamaker, B. R. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.01.08.523060
García‐Alonso, Y. (2023) · Academica-e (Universidad Pública de Navarra) · doi:10.48035/tesis/2454/45481
Wang, Z., Sun, Y., Chen, X., Gong, P., Gao, F., Yao, W., Ba, Q., & Wang, H. (2023) · SSRN Electronic Journal · doi:10.2139/ssrn.4510736
METABOLIC SYNDROME RELATIONSHIP AND RISK FACTORS ASSOCIATED WITH IMMEDIATE LIFE PATH ENVIRONMENTS
Jefferson, J. (2024) · Health and Society · doi:10.51249/hs.v4i02.1966
Santos, A. F. D. S. (2020) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.17.2020.tde-17072024-161003
Achmat, G., Malema, M. J., Erasmus, C. J., Kanaley, J. A., & Leach, L. L. (2024) · The Open Public Health Journal · doi:10.2174/0118749445327343240821051143 · Cited by 1
Jiang, L., Lu, X., Lin, X., Cao, Z., Liu, R., Mu, G., & Jiang, S. (2024) · Food Science and Human Wellness · doi:10.26599/fshw.2024.9250406
Ahamad, R., Ali, A., Manna, P., Quadri, N., Khan, Z., Pal, R., Muztaba, M., Ghazanfar, S., Islam, A., Iqbal, A., et al. (2025) · Wiley eBooks · doi:10.1002/9781394313785.ch10
Sun, Y., Ni, W., Yuan, X., 池洪珊, & Xu, J. (2020) · Figshare · doi:10.6084/m9.figshare.12569675
Wahaibi, A. A., Lawati, A. A., Hinai, M. A., Hadhrami, A. A., AlRuheili, I., AlMusallami, M. S., Lawati, H. A., & Das, S. (2026) · Mini-Reviews in Medicinal Chemistry · doi:10.2174/0113895575423784251206060716
Liu, Y., Wu, J., Li, N., Zhang, S., Feng, Y., Zhang, Y., & Shao, Y. (2026) · Nutrition & Metabolism · doi:10.1186/s12986-026-01114-3
Zazula, M. F., Carvalhal, S. R. S., Maciel, D. T., Moritz, D., Beirauti, H. Y. I., Amorim, L., Rocha, M. T., Maciel, M., Sales, O., Dobgenski, P., et al. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27136049
Meshkat, K., Gijbels, A., Afman, L. A., Goossens, G. H., Blaak, E. E., & Meex, R. C. R. (2026) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2026.113480
Self-citationOstrowicz, K., Brzuchacz, D., Malinowski, A., Pelczar, A. K., Oczkowska, W., Marchewka, K., Ciesielska, J., Furtek, D., Bartosik, K., & Borkowska, J. (2026) · International Journal of Innovative Technologies in Social Science · doi:10.31435/ijitss.3(51).2026.6684
Vilarinho, R. (2015) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT)
Metadata
- Authors
- Corpeleijn, E., Saris, W. H. M., & Blaak, E. E.
- Affiliations
- Maastricht University (NL)
- Corresponding author
- Corpeleijn, E.
- Venue
- Obesity Reviews
- Publisher
- Wiley
- Published
- 2009-02-23
- Volume
- 10
- Issue
- 2
- Pages
- 178-193
- ISSN
- 1467-7881 (ISSN-L)
- 1467-789X
- OpenAlex
- W2016142529
- Cited by
- 280
- References
- 112
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 11 · 2023: 12 · 2022: 16 · 2021: 17 · 2020: 15 · 2019: 13 · 2018: 10 · 2017: 22 · 2016: 21 · 2015: 18 · 2014: 19 · 2013: 21 · 2012: 16
- FWCI
- 1.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Obesity Reviews (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- metabolic flexibility, insulin resistance, type 2 diabetes, lipotoxicity, skeletal muscle, fatty acid oxidation, fat oxidation, fatty acid uptake, fatty acid transporters, mitochondrial function, fuel switching, dietary fat intake, physical activity, weight loss, lifestyle intervention
- MeSH terms
- Animals, Diabetes Mellitus, Type 2, Diet, Energy Metabolism, Fatty Acids, Humans, Insulin Resistance, Life Style, Oxidation-Reduction, Weight Loss, Exercise, Muscle, Skeletal
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
