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.
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“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
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Short-chain fatty acids in control of body weight and insulin sensitivity
Canfora, E. E., Jocken, J. W., & Blaak, E. E. (2015) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.128 · Cited by 2,298
Self-citationGut microbial metabolites in obesity, NAFLD and T2DM
Canfora, E. E., Meex, R. C. R., Venema, K., & Blaak, E. E. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0156-z · Cited by 1,493
Self-citationTrends in insulin resistance: insights into mechanisms and therapeutic strategy
Li, M., Chi, X., Wang, Y., Setrerrahmane, S., Xie, W., & Xu, H. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01073-0 · Cited by 939
The role of the gut microbiome and its metabolites in metabolic diseases
Wu, J., Wang, K., Wang, X., Pang, Y., & Jiang, C. (2020) · Protein & Cell · doi:10.1007/s13238-020-00814-7 · Cited by 592
Dietary Strategies for Metabolic Syndrome: A Comprehensive Review
Castro‐Barquero, S., Ruiz-León, A. M., Sierra-Pérez, M., Estruch, R., & Casas, R. M. (2020) · Nutrients · doi:10.3390/nu12102983 · Cited by 530
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
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