ArticleThe Journal of biological chemistry2016
A Role for Ceramides, but Not Sphingomyelins, as Antagonists of Insulin Signaling and Mitochondrial Metabolism in C2C12 Myotubes.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 3 of them syntheses that pooled it.
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The trial behind it
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
53 citing papers in PubMed, 3 syntheses or guidelines pooled it, 80 citations in OpenAlex.
- Sphingolipids associated research in Alzheimer's disease: an explored trends analysis.Frontiers in aging neuroscience · 2026Pooled it
- Pooled it
- The Role of Fatty Acids in Ceramide Pathways and Their Influence on Hypothalamic Regulation of Energy Balance: A Systematic Review.International journal of molecular sciences · 2021Pooled it
- Trial
- Intracellular localization of diacylglycerols and sphingolipids influences insulin sensitivity and mitochondrial function in human skeletal muscle.JCI insight · 2018Trial
- Machine learning identifies plasma-derived exosomal miRNAs associated with low muscle mass in Tibetan patients with rheumatoid arthritis.Scientific reports · 2026Article
- Sphingolipid Metabolism in Obesity: Bidirectional Regulation and Comparative Perspectives on Plant Sphingolipids.Nutrients · 2026Review
- Ceramide metabolism in oxidative and glycolytic muscle: Significance for lipid-induced insulin resistance.Molecular metabolism · 2026Article
- Sphingolipids in human disease: organ-specific pathologies, chain-length-dependent effects, and translational implications.Journal of translational medicine · 2026Review
- Detergents without a drain: the evolutionary logic (and liability) of sphingolipids.Journal of lipid research · 2026Review
- Adipose tissue ceramides: emerging lipid components of extracellular vesicles and their influence on metabolic dysregulation.Frontiers in endocrinology · 2026Review
- Integrative multi-omics analysis of metabolic dysregulation induced by occupational benzene exposure in mice.The Science of the total environment · 2025Article
- Sphingolipid Metabolism and Signalling Pathways in Heart Failure: From Molecular Mechanism to Therapeutic Potential.Journal of inflammation research · 2025Review
- Ceramide microdomains: the major influencers of the sphingolipid media platform.Biochemical Society transactions · 2024Review
- Sphingolipid Metabolism Is Associated with Cardiac Dyssynchrony in Patients with Acute Myocardial Infarction.Biomedicines · 2024Article
- Ceramides are fuel gauges on the drive to cardiometabolic disease.Physiological reviews · 2024Review
- Inhibition ofeLife · 2024Article
- Association between relative muscle strength and hypertension in middle-aged and older Chinese adults.BMC public health · 2023Article
- Palmitate-Induced Inflammation and Myotube Atrophy in C2C12 Cells Are Prevented by the Whey Bioactive Peptide, Glycomacropeptide.The Journal of nutrition · 2023Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The accumulation of sphingolipids in obesity leads to impairments in insulin sensitivity and mitochondrial metabolism, but the precise species driving these defects is unclear. We have modeled these obesity-induced effects in cultured C2C12 myotubes, using BSA-conjugated palmitate to increase synthesis of endogenous sphingolipids and to inhibit insulin signaling and oxidative phosphorylation. Palmitate (a) induced the accumulation of sphingomyelin (SM) precursors such as sphinganine, dihydroceramide, and ceramide; (b) inhibited insulin stimulation of a central modulator of anabolic metabolism, Akt/PKB; (c) inhibited insulin-stimulated glycogen synthesis; and (d) decreased oxygen consumption and ATP synthesis. Under these conditions, palmitate failed to alter levels of SMs, which are the most abundant sphingolipids, suggesting that they are not the primary intermediates accounting for the deleterious palmitate effects. Treating cells with a pharmacological inhibitor of SM synthase or using CRISPR to knock out the Sms2 gene recapitulated the palmitate effects by inducing the accumulation of SM precursors and impairing insulin signaling and mitochondrial metabolism. To profile the sphingolipids that accumulate in obesity, we performed lipidomics on quadriceps muscles from obese mice with impaired glucose tolerance. Like the cultured myotubes, these tissues accumulated ceramides but not SMs. Collectively, these data suggest that SM precursors such as ceramides, rather than SMs, are likely nutritional antagonists of metabolic function in skeletal muscle.
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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.