ArticleDiabetologia2024
Oxidised phosphatidylcholine induces sarcolemmal ceramide accumulation and insulin resistance in skeletal muscle.
Article in Diabetologia, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Exercise-Induced Regulation of Spexin: Implications for Metabolic Health: A Systematic Review and Meta-Analysis.Medicina (Kaunas, Lithuania) · 2026Pooled it
- Oxidized Phosphatidylcholines Regulate Secretory Phospholipase AMolecules (Basel, Switzerland) · 2026Article
- Insulin resistance: mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- Article
- Association of magnesium depletion score, triglyceride-glucose index, and C-reactive protein-albumin-lymphocyte index with diabetic sarcopenia: a cross-sectional study based on NHANES 2014-2018 data.American journal of translational research · 2026Article
- Structural Insights into Recognition and Translocation of Oxidized Phospholipid by CD36 Using Mass Spectrometry, Molecular Docking, Dynamics, and Metadynamics Simulations.Journal of the American Chemical Society · 2025Article
- Impact of Lipid Oxidation Products on Inflammation and Insulin Resistance: A Focus on Mechanisms of Action.Cell biochemistry and biophysics · 2025Review
- Redox Homeostasis in Metabolic Syndrome and Type II Diabetes: Role of Skeletal Muscle and Impact of Gold-Standard Treatments.International journal of molecular sciences · 2025Review
- Article
- A Review Discussing Synthesis and Translational Studies of Medicinal Agents Targeting Sphingolipid Pathways.Biomolecules · 2025Review
- Article
- Muscle quality index and hyperuricemia: adipose tissue as a mediator.Frontiers in endocrinology · 2025Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
aims/hypothesisIntracellular ceramide accumulation in specific cellular compartments is a potential mechanism explaining muscle insulin resistance in the pathogenesis of type 2 diabetes. Muscle sarcolemmal ceramide accumulation negatively impacts insulin sensitivity in humans, but the mechanism explaining this localised accumulation is unknown. Previous reports revealed that circulating oxidised LDL is elevated in serum of individuals with obesity and type 2 diabetes. Oxidised phosphatidylcholine, which is present in oxidised LDL, has previously been linked to ceramide pathway activation, and could contribute to localised ceramide accumulation in skeletal muscle. We hypothesised that oxidised phosphatidylcholine inversely correlates with insulin sensitivity in serum, and induces sarcolemmal ceramide accumulation and decreases insulin sensitivity in muscle.
methodsWe used LC-MS/MS to quantify specific oxidised phosphatidylcholine species in serum from a cross-sectional study of 58 well-characterised individuals spanning the physiological range of insulin sensitivity. We also performed in vitro experiments in rat L6 myotubes interrogating the role of specific oxidised phosphatidylcholine species in promoting sarcolemmal ceramide accumulation, inflammation and insulin resistance in skeletal muscle cells.
resultsHuman serum oxidised phosphatidylcholine levels are elevated in individuals with obesity and type 2 diabetes, inversely correlated with insulin sensitivity, and positively correlated with sarcolemmal C18:0 ceramide levels in skeletal muscle. Specific oxidised phosphatidylcholine species, particularly 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC), increase total ceramide and dihydroceramide and decrease total sphingomyelin in the sarcolemma of L6 myotubes by de novo ceramide synthesis and sphingomyelinase activation. POVPC also increases inflammatory signalling and causes insulin resistance in L6 myotubes. CONCLUSIONS/
interpretationThese data suggest that circulating oxidised phosphatidylcholine species promote ceramide accumulation and decrease insulin sensitivity in muscle, help explain localised sphingolipid accumulation and muscle inflammatory response, and highlight oxidised phosphatidylcholine species as potential targets to combat insulin resistance.
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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 Socratic graph.