Mitofusin 2 deficiency leads to oxidative stress that contributes to insulin resistance in rat skeletal muscle cells
Abstract
Mitofusin 2 (Mfn2) is a dynamin-like protein anchored in the outer mitochondrial membrane that plays a crucial role in ensuring optimal mitochondrial morphological homeostasis. It has been shown that reduced expression of Mfn2 is associated with insulin resistance, but the mechanism is still unclear. We investigated whether Mfn2 deficiency leads to impaired insulin sensitivity via elevated oxidative stress. L6 skeletal muscle cells were treated with palmitate and Mfn2 expression was repressed by transfection with antisense Mfn2. Levels of antioxidant enzymes, reactive oxygen species (ROS), the phosphorylation of c-Jun N-terminal Kinase (JNK) and nuclear factor-κB (NF-κB) and the mitochondrial membrane potential (Δψm) were measured. The results showed palmitate-induced insulin resistance of skeletal muscle cells was accompanied by Mfn2 repression. Meanwhile, the cells had decreased Δψm and activity of antioxidant enzymes which could increase production of ROS, phosphorylation of JNK and NF-κB. When Mfn2 was up-regulated in palmitate-treated cells, oxidative stress and insulin resistance was alleviated. Furthermore, knock-down of Mfn2 in control cells enhanced oxidative stress. Mfn2 deficiency led to increased superoxide concentration and activation of JNK as well as NF-κB associated with insulin signaling. In conclusion, Mfn2 is a potent repressor for oxidative stress and regulation of Mfn2 expression may prove to be a potential method to circumvent insulin resistance.
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Nie et al. reported that Mfn2-deficient mice display impaired insulin sensitivity attributed to elevated oxidative stress.
“Nie et al. reported that Mfn2-deficient mice display impaired insulin sensitivity attributed to elevated oxidative stress [47].”
From Mitochondrial Adaptation in Skeletal Muscle: Impact of Obesity, Caloric Restriction, and Dietary Compounds (2024) · cites this paper as [47]
In L6 cells treated with palmitate and siMfn2, repression of Mfn2 mRNA expression coincides with reduced mitochondrial membrane potential and antioxidant enzyme activities, resulting in elevated ROS production and phosphorylation of inflammatory cytokines.
“In L6 cells treated with palmitate and small interfering RNA (siMfn2), repression of Mfn2 mRNA expression coincides with reduced mitochondrial membrane potential and antioxidant enzyme activities, resulting in elevated ROS production and the phosphorylation of inflammatory cytokines.”
From Mitochondrial Adaptation in Skeletal Muscle: Impact of Obesity, Caloric Restriction, and Dietary Compounds (2024) · cites this paper as [47]
Upon reintroduction of MFN2, oxidative stress and insulin resistance are alleviated.
“Upon reintroduction of MFN2, the oxidative stress and insulin resistance are alleviated [47].”
From Mitochondrial Adaptation in Skeletal Muscle: Impact of Obesity, Caloric Restriction, and Dietary Compounds (2024) · cites this paper as [47]
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- Authors
- Nie, Q., Wang, C., Song, G., Ma, H., Kong, D., Zhang, X., Gan, K., & Tang, Y.
- Affiliations
- Hebei Medical University (CN)
- Hebei General Hospital (CN)
- Corresponding author
- Song, Guangyao
- Venue
- Molecular Biology Reports
- Published
- 2014-07-18
- Volume
- 41
- Issue
- 10
- Pages
- 6975-6983
- ISSN
- 0301-4851 (ISSN-L)
- 1573-4978
- OpenAlex
- W2002460545
- Cited by
- 47
- References
- 28
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 4 · 2022: 4 · 2021: 5 · 2020: 4 · 2019: 3 · 2018: 7 · 2017: 4 · 2016: 3 · 2015: 7 · 2014: 1
- FWCI
- 2.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Molecular Biology Reports (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- mitofusin 2, insulin resistance, oxidative stress, skeletal muscle cells, palmitate, reactive oxygen species, mitochondrial membrane potential, JNK phosphorylation, NF-κB, antioxidant enzymes, mitochondrial fusion, insulin signaling
- MeSH terms
- Animals, Antioxidants, Cell Line, Gene Expression Regulation, Glucose, Insulin Resistance, Membrane Proteins, Palmitates, Phosphorylation, Signal Transduction, NF-kappa B, Reactive Oxygen Species, Oxidative Stress, Muscle Fibers, Skeletal, GTP Phosphohydrolases, Mitochondrial Proteins, JNK Mitogen-Activated Protein Kinases, Rats, Membrane Potential, Mitochondrial
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