ArticleCellular and molecular life sciences : CMLS2019
Proinflammatory NFkB signalling promotes mitochondrial dysfunction in skeletal muscle in response to cellular fuel overloading.
Article in Cellular and molecular life sciences : CMLS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.
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Who cites it
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 130 citations in OpenAlex.
- The crucial role and mechanism of insulin resistance in metabolic disease.Frontiers in endocrinology · 2023Pooled it
- Pancreatic Cancer Disrupts Circadian Patterns of Gene Expression in Cardiorespiratory Muscles.Journal of cachexia, sarcopenia and muscle · 2026Article
- Immunometabolic Plasticity in Sarcopenic Obesity: Toward a New Paradigm for Precision Immunonutrition.Nutrients · 2026Review
- Exercise as a Molecular Therapeutic Strategy in Metabolic Syndrome: Integrating Cellular Signaling, Organ Crosstalk, and Clinical Translation-A Narrative Review.Current issues in molecular biology · 2026Review
- Review
- PDLIM2 acts as a central regulator of ubiquitination, immune signaling, and mitochondrial metabolism in lung cancer suppression (Review).International journal of oncology · 2026Review
- Modulation of NFκB Signaling by Natural Compounds in Sarcoma and Normal Muscle Models.International journal of molecular sciences · 2026Article
- Induction of mitochondrial fission and mtDNA leakage via the Smad3/Drp1 axis by PEDV infection activates the TLR9/NF-κB/IL-1β inflammatory pathway.Virologica Sinica · 2026Article
- Transcriptome and experimental validation identify prognostic genes associated with lipotoxicity in thyroid carcinoma.BMC cancer · 2026Article
- Sprouted Wheat Improves Liver Metabolism and Inflammation in T2DM Mice: 16S rRNA Gene Sequence, Metabolomics and Network Pharmacology Joint Analysis.Foods (Basel, Switzerland) · 2026Article
- Cellular Anti-Apoptotic Effects of Dapagliflozin in Methotrexate-Induced Liver Toxicity: Bax/Bcl-2/Cyt-C/Cas-9/Cas-3 Signaling Pathway.International journal of molecular sciences · 2026Article
- The organelle oxidative-inflammatory network in polycystic ovary syndrome: from subcellular intercellular cascades to systemic comorbidities.Frontiers in immunology · 2026Review
- Association of the hs-CRP-TyG index with coronary artery disease risk and angiographic severity: a retrospective comparative study with the TyG index.Frontiers in endocrinology · 2026Article
- Spatial-Bioenergetic-Immune Axis in Type 2 Diabetes Mellitus-Associated Sarcopenia: A Review from Pathogenesis to Targeted Reconstruction.Journal of inflammation research · 2026Review
- The inflammatory clock: how cGAS-STING ticks in the aging ovary.Frontiers in cell and developmental biology · 2026Review
- Mitochondrial complex III-derived ROS amplify immunometabolic changes in astrocytes and promote dementia pathology.Nature metabolism · 2025Article
- Skeletal muscle atrophy and dysfunction in obesity and type-2 diabetes mellitus: Myocellular mechanisms involved.Reviews in endocrine & metabolic disorders · 2025Review
- Maternal Nutrient Excess Induces Stress Signaling and Decreases Mitochondrial Number in Term Fetal Baboon Skeletal Muscle.Biology · 2025Article
- Anti-Obesity Effects ofFood science & nutrition · 2025Article
- Phosphodiesterase 7: a potential novel therapeutic target in ovarian cancer.Frontiers in pharmacology · 2025Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Sustained nutrient (fuel) excess, as occurs during obesity and diabetes, has been linked to increased inflammation, impaired mitochondrial homeostasis, lipotoxicity, and insulin resistance in skeletal muscle. Precisely how mitochondrial dysfunction is initiated and whether it contributes to insulin resistance in this tissue remains a poorly resolved issue. Herein, we examine the contribution that an increase in proinflammatory NFkB signalling makes towards regulation of mitochondrial bioenergetics, morphology, and dynamics and its impact upon insulin action in skeletal muscle cells subject to chronic fuel (glucose and palmitate) overloading. We show sustained nutrient excess of L6 myotubes promotes activation of the IKKβ-NFkB pathway (as judged by a six-fold increase in IL-6 mRNA expression; an NFkB target gene) and that this was associated with a marked reduction in mitochondrial respiratory capacity (>50%), a three-fold increase in mitochondrial fragmentation and 2.5-fold increase in mitophagy. Under these circumstances, we also noted a reduction in the mRNA and protein abundance of PGC1α and that of key mitochondrial components (SDHA, ANT-1, UCP3, and MFN2) as well as an increase in cellular ROS and impaired insulin action in myotubes. Strikingly, pharmacological or genetic repression of NFkB activity ameliorated disturbances in mitochondrial respiratory function/morphology, attenuated loss of SDHA, ANT-1, UCP3, and MFN2 and mitigated the increase in ROS and the associated reduction in myotube insulin sensitivity. Our findings indicate that sustained oversupply of metabolic fuel to skeletal muscle cells induces heightened NFkB signalling and that this serves as a critical driver for disturbances in mitochondrial function and morphology, redox status, and insulin signalling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.