Cited by 280Metabolism, Diabetes, and CancerAdipose Tissue and MetabolismDiabetes, Cardiovascular Risks, and Lipoproteins

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Metabolic flexibility in the development of insulin resistance and type 2 diabetes: effects of lifestyle

Corpeleijn, E., Saris, W. H. M., Blaak, E. E.·2009·Obesity Reviews

DOI 10.1111/j.1467-789x.2008.00544.x

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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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Authors: Corpeleijn, E., Saris, W. H. M., & Blaak, E. E.
Affiliations: Maastricht University (NL)
Corresponding author: Corpeleijn, E.
ORCID: Corpeleijn, E.
Saris, W. H. M.
Blaak, E. E.
Venue: Obesity Reviews
Publisher: Wiley
Published: 2009-02-23
Volume: 10
Issue: 2
Pages: 178-193
ISSN: 1467-7881 (ISSN-L)
1467-789X
DOI: 10.1111/j.1467-789x.2008.00544.x
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
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
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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Metabolic flexibility in the development of insulin resistance and type 2 diabetes: effects of lifestyle

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