Saturated fatty acid‐induced insulin resistance is associated with mitochondrial dysfunction in skeletal muscle cells
Open accessAbstract
Increased plasma levels of free fatty acids (FFA) occur in states of insulin resistance such as obesity and type 2 diabetes mellitus. These high levels of plasma FFA are proposed to play an important role for the development of insulin resistance but the mechanisms involved are still unclear. This study investigated the effects of saturated and unsaturated FFA on insulin sensitivity in parallel with mitochondrial function. C2C12 myotubes were treated for 24 h with 0.1 mM of saturated (palmitic and stearic) and unsaturated (oleic, linoleic, eicosapentaenoic, and docosahexaenoic) FFA. After this period, basal and insulin‐stimulated glucose metabolism and mitochondrial function were evaluated. Saturated palmitic and stearic acids decreased insulin‐induced glycogen synthesis, glucose oxidation, and lactate production. Basal glucose oxidation was also reduced. Palmitic and stearic acids impaired mitochondrial function as demonstrated by decrease of both mitochondrial hyperpolarization and ATP generation. These FFA also decreased Akt activation by insulin. As opposed to saturated FFA, unsaturated FFA did not impair glucose metabolism and mitochondrial function. Primary cultures of rat skeletal muscle cells exhibited similar responses to saturated FFA as compared to C2C12 cells. These results show that in muscle cells saturated FFA‐induced mitochondrial dysfunction associated with impaired insulin‐induced glucose metabolism. J. Cell. Physiol. 222:187–194, 2010. © 2009 Wiley‐Liss, Inc.
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Unsaturated and ω-3 polyunsaturated FFAs do not alter mitochondrial membrane potential and ATP generation in C2C12 cells.
“For example, saturated FAs reduce mitochondrial membrane potential, as well as ATP generation, in C2C12 cells, while unsaturated and ω-3 polyunsaturated FFAs do not alter these functions (21).”
From Mitochondrial Fission Contributes to Mitochondrial Dysfunction and Insulin Resistance in Skeletal Muscle (2012) · cites this paper as [21]
Saturated FAs reduce mitochondrial membrane potential, as well as ATP generation, in C2C12 cells.
“For example, saturated FAs reduce mitochondrial membrane potential, as well as ATP generation, in C2C12 cells, while unsaturated and ω-3 polyunsaturated FFAs do not alter these functions (21).”
From Mitochondrial Fission Contributes to Mitochondrial Dysfunction and Insulin Resistance in Skeletal Muscle (2012) · cites this paper as [21]
In the C2C12 muscle cell line, both palmitic and stearic acid challenge induce mitochondrial dysfunction characterised by mitochondria membrane hyperpolarisation and defective ATP generation.
“The effect of long-chain saturated fatty acids was confirmed in C2C12 muscle cell line in which both palmitic and stearic acid challenge induced mitochondrial dysfunction characterised by mitochondria membrane hyperpolarisation and defective ATP generation (Hirabara et al., 2010).”
From Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet (2019) · cites this paper as Hirabara et al., 2010
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- Authors
- Hirabara, S. M., Curi, R., & Maechler, P.
- Affiliations
- University of Geneva (CH)
- Universidade de São Paulo (BR)
- Corresponding author
- Hirabara, Sandro M.
- Venue
- Journal of Cellular Physiology
- Publisher
- Wiley
- Published
- 2009-09-24
- Volume
- 222
- Issue
- 1
- Pages
- 187-194
- ISSN
- 0021-9541 (ISSN-L)
- 1097-4652
- OpenAlex
- W2073795408
- Semantic Scholar
- b5681ae8eecef2c20d7de77bedc73116ba1f03f7
- Cited by
- 215
- References
- 62
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 8 · 2023: 11 · 2022: 9 · 2021: 10 · 2020: 13 · 2019: 13 · 2018: 12 · 2017: 16 · 2016: 11 · 2015: 19 · 2014: 20 · 2013: 18 · 2012: 21
- FWCI
- 5.23
- Type
- journal article
- Language
- en
- Open access
- Locations
- Journal of Cellular Physiology (publishedVersion)
- PubMed (publishedVersion)
- Scientific Electronic Library Online (São Paulo Research Foundation, Latin American and Caribbean Center on Health Sciences Information, Conselho Nacional de Desenvolvimento Científico e Tecnológico) (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- saturated fatty acids, insulin resistance, mitochondrial dysfunction, skeletal muscle, free fatty acids, palmitic acid, stearic acid, unsaturated fatty acids, glucose metabolism, glucose oxidation, glycogen synthesis, lactic acid production, mitochondrial hyperpolarization, ATP production, Akt activation, C2C12 myotubes, type 2 diabetes, obesity
- MeSH terms
- Adenosine Triphosphate, Animals, Cell Survival, Cells, Cultured, Fatty Acids, Glucose, Insulin, Insulin Resistance, Mitochondria, Oligomycins, Phosphorylation, Stearic Acids, Rats, Wistar, Muscle, Skeletal, Muscle Fibers, Skeletal, Palmitic Acid, Muscle Cells, Proto-Oncogene Proteins c-akt, Mice, Rats, Membrane Potential, Mitochondrial
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