ArticleAmerican journal of physiology. Endocrinology and metabolism2015
Long-chain acylcarnitines activate cell stress and myokine release in C2C12 myotubes: calcium-dependent and -independent effects.
Article in American journal of physiology. Endocrinology and metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Causal relationships of metabolites with allergic diseases: a trans-ethnic Mendelian randomization study.Respiratory research · 2024Pooled it
- Vaginal lipidomics of women with vulvovaginal candidiasis and cytolytic vaginosis: A non-targeted LC-MS pilot study.PloS one · 2018Trial
- Chemical-Specific Metabolic Disruption during Early Zebrafish Development is Modulated by the Microbiome.Environment & health (Washington, D.C.) · 2026Article
- Maximizing Lipidome Coverage of Mouse Liver Following the IV Administration of Gefitinib by Combining Both UHPLC-MS-Based Untargeted and Targeted Lipidomics.Journal of proteome research · 2026Article
- Serum acylcarnitine to amide ratio as a predictive biomarker for the progression of pulmonary disease caused byERJ open research · 2026Article
- Gliquidone alleviates DSS-induced ulcerative colitis in rats by targeting carnitine palmitoyltransferase 1A.Journal of pharmaceutical analysis · 2026Article
- Androgen Receptors Promote Oxidative Phosphorylation and Resistance to Palmitate Lipotoxicity in ER-Mutant Breast Cancer.Endocrinology · 2025Article
- Acylcarnitine enrichment as a characteristic of rheumatoid arthritis fibroblast-like synoviocyte metabolic fingerprint.Journal of translational autoimmunity · 2025Article
- Harnessing Metabolomics to Advance Nutrition-Based Therapeutics for Inflammation: A Systematic Review of Randomized Clinical Trials.Metabolites · 2025Review
- The role of carnitine palmitoyl transferase 2 in the progression of salt-sensitive hypertension.American journal of physiology. Cell physiology · 2025Article
- Reveals meat quality and muscle metabolism characteristics in naturally grazed Sunit sheep at different ages.Food chemistry: X · 2025Article
- Cold operational readiness in the military: from science to practice.BMJ military health · 2025Review
- Comprehensive review of the expanding roles of the carnitine pool in metabolic physiology: beyond fatty acid oxidation.Journal of translational medicine · 2025Review
- Metabolomic profiles of stony coral species from the Dry Tortugas National Park display inter- and intraspecies variation.mSystems · 2024Article
- Identifying the Shared Metabolite Biomarkers and Potential Intervention Targets for Multiple Sarcopenia-Related Phenotypes.International journal of molecular sciences · 2024Article
- A versatile delivery vehicle for cellular oxygen and fuels or metabolic sensor? A review and perspective on the functions of myoglobin.Physiological reviews · 2024Review
- Comparative analysis of circulating metabolomic profiles identifies shared metabolic alterations across distinct multistressor military training exercises.Physiological genomics · 2024Article
- Article
- A Distinctive Metabolomics Profile and Potential Biomarkers for Very Long Acylcarnitine Dehydrogenase Deficiency (VLCADD) Diagnosis in Newborns.Metabolites · 2023Article
- CPT2 K79 acetylation regulates platelet life span.Blood advances · 2022Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
Acylcarnitines, important lipid biomarkers reflective of acyl-CoA status, are metabolites that possess bioactive and inflammatory properties. This study examined the potential for long-chain acylcarnitines to activate cellular inflammatory, stress, and death pathways in a skeletal muscle model. Differentiated C2C12 myotubes treated with l-C14, C16, C18, and C18:1 carnitine displayed dose-dependent increases in IL-6 production with a concomitant rise in markers of cell permeability and death, which was not observed for shorter chain lengths. l-C16 carnitine, used as a representative long-chain acylcarnitine at initial extracellular concentrations ≥25 μM, increased IL-6 production 4.1-, 14.9-, and 31.4-fold over vehicle at 25, 50, and 100 μM. Additionally, l-C16 carnitine activated c-Jun NH2-terminal kinase, extracellular signal-regulated kinase, and p38 mitogen-activated protein kinase between 2.5- and 11-fold and induced cell injury and death within 6 h with modest activation of the apoptotic caspase-3 protein. l-C16 carnitine rapidly increased intracellular calcium, most clearly by 10 μM, implicating calcium as a potential mechanism for some activities of long-chain acylcarnitines. The intracellular calcium chelator BAPTA-AM blunted l-C16 carnitine-mediated IL-6 production by >65%. However, BAPTA-AM did not attenuate cell permeability and death responses, indicating that these outcomes are calcium independent. The 16-carbon zwitterionic compound amidosulfobetaine-16 qualitatively mimicked the l-C16 carnitine-associated cell stress outcomes, suggesting that the effects of high experimental concentrations of long-chain acylcarnitines are through membrane disruption. Herein, a model is proposed in which acylcarnitine cell membrane interactions take place along a spectrum of cellular concentrations encountered in physiological-to-pathophysiological conditions, thus regulating function of membrane-based systems and impacting cell biology.
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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.