Cited by 48Mitochondrial Function and PathologyMetabolism, Diabetes, and CancerAdipose Tissue and Metabolism

Mitofusin 2 deficiency leads to oxidative stress that contributes to insulin resistance in rat skeletal muscle cells

Nie, Qian, Wang, Chao, Song, Guangyao, Ma, Huijuan, Kong, Dexian, Zhang, Xuemei, Gan, Kexin, Tang, Yong·2014·Molecular Biology Reports

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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Crossref · 10.1007/s11033-014-3584-9

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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
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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