ArticleNature communications2022
Long-chain ceramides are cell non-autonomous signals linking lipotoxicity to endoplasmic reticulum stress in skeletal muscle.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 63 citations in OpenAlex.
- Trial
- CerS2-mediated lipotoxicity and calcium signaling: a novel sequential mechanism of apoptosis in cancer.The Biochemical journal · 2026Review
- Hepatic HIF2α Modulates Extra-Hepatic Disease-Associated Phenotypes During Metabolic Dysfunction-Associated Steatotic Liver Disease.Comprehensive physiology · 2026Article
- Skeletal Muscle-Derived Extracellular Vesicles in Interorgan Communication During Aging.Aging cell · 2026Review
- Sphingolipid Remodeling and Extracellular Vesicle Signatures Reflect Disease Severity in Facioscapulohumeral Dystrophy Driven by Mitochondrial Dysfunction and Endoplasmic Reticulum Stress.Antioxidants (Basel, Switzerland) · 2026Article
- Apical proximal tubule fatty acid uptake-generated ceramides cause endoplasmic reticulum stress from altered membrane fluidity.JCI insight · 2026Article
- Integrative multi-omics analyses reveal the molecular mechanisms of lysozyme in alleviating hepatic lipid accumulation in post-peak laying quail.Poultry science · 2026Article
- Ceramide-Driven Mechanisms in Pulmonary Fibrosis.Metabolites · 2026Review
- Review
- Inhibition of ceramide synthesis ameliorates body wasting in a cancer cachexia model.The Journal of clinical investigation · 2026Article
- Curcumin as a ceramide metabolism-targeting agent: Molecular mechanisms and therapeutic implications in cancer.Molecular biology reports · 2026Review
- Dynamic Lipidomic Responses to Inflammation and Physical Insult: A Comparative Review Across Blunt Force Trauma, Thermal Burn Injury, and Viral Infection.Expert reviews in molecular medicine · 2026Review
- Article
- Article
- Adaptive inter-tissue proteostasis networks in aging and neurodegeneration.Bioscience reports · 2026Review
- The dysregulated unfolded protein response in diabetic kidney disease: mechanisms and crosstalk with cell death pathways.Frontiers in pharmacology · 2026Review
- "Seipin mediates Perilipin-1 recruitment to lipid droplets to preserve human adipocyte identity".bioRxiv : the preprint server for biology · 2025Article
- Role of nuclear receptors, lipid metabolism, and mitochondrial function in the pathogenesis of diabetic kidney disease.American journal of physiology. Renal physiology · 2025Review
- Human-induced pluripotent stem cell-based hepatic modeling of lipid metabolism-associated TM6SF2-E167K variant.Hepatology (Baltimore, Md.) · 2025Article
- Palmitate enhances MSC immunomodulation of human macrophages via the ceramide/CCL2 axis in vitro.Stem cell research & therapy · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 4 institutions in 3 countries.
Funding
Abstract
The endoplasmic reticulum (ER) regulates cellular protein and lipid biosynthesis. ER dysfunction leads to protein misfolding and the unfolded protein response (UPR), which limits protein synthesis to prevent cytotoxicity. Chronic ER stress in skeletal muscle is a unifying mechanism linking lipotoxicity to metabolic disease. Unidentified signals from cells undergoing ER stress propagate paracrine and systemic UPR activation. Here, we induce ER stress and lipotoxicity in myotubes. We observe ER stress-inducing lipid cell non-autonomous signal(s). Lipidomics identifies that palmitate-induced cell stress induces long-chain ceramide 40:1 and 42:1 secretion. Ceramide synthesis through the ceramide synthase 2 de novo pathway is regulated by UPR kinase Perk. Inactivation of CerS2 in mice reduces systemic and muscle ceramide signals and muscle UPR activation. The ceramides are packaged into extracellular vesicles, secreted and induce UPR activation in naïve myotubes through dihydroceramide accumulation. This study furthers our understanding of ER stress by identifying UPR-inducing cell non-autonomous signals.
Indexed as
Identifiers
What OpenQuestion holds
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.