ArticleThe Journal of clinical investigation2012
Ceramide synthase 5 mediates lipid-induced autophagy and hypertrophy in cardiomyocytes.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
137 citing papers in PubMed, 1 synthesis or guideline pooled it, 203 citations in OpenAlex.
- Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension.Nature genetics · 2016Pooled it
- Alterations in plasma triglycerides and ceramides: links with cardiac function in humans with type 2 diabetes.Journal of lipid research · 2020Trial
- A Diet Rich in Medium-Chain Fatty Acids Improves Systolic Function and Alters the Lipidomic Profile in Patients With Type 2 Diabetes: A Pilot Study.The Journal of clinical endocrinology and metabolism · 2016Trial
- Lipid-manager autophagy proteins ATG2 and ATG9 regulate extracellular vesicle secretion via amphisome biogenesis and cell lipidome modulation.Nature communications · 2026Article
- Cardiac Lipid Metabolism: Cells, Metabolites, and Rhythms.Circulation research · 2026Review
- Western diet-induced MASH in PWK/PhJ mice identifies disruptions in amino acid and sphingolipid metabolism contributing to cardiac dysfunction.Nature communications · 2026Article
- Review
- The Role of Ceramides in Metabolic and Cardiovascular Diseases.Journal of cardiovascular development and disease · 2026Review
- Deciphering the Role of Different Ceramide Synthases in the Human Cardiomyocyte Hypertrophic Response.Metabolites · 2025Article
- Article
- Novel cardiac biomarkers and multiple-marker approach in the early detection, prognosis, and risk stratification of cardiac diseases.World journal of cardiology · 2025Review
- Ceramide Synthase 2 Promotes Cardiac Very-Long-Chain Dihydroceramide Accumulation and Is Linked to Arrhythmias and Heart Failure in Humans.International journal of molecular sciences · 2025Article
- The role of sphingolipids in heart failure.European heart journal open · 2025Review
- Metabolic and Mitochondrial Dysregulations in Diabetic Cardiac Complications.International journal of molecular sciences · 2025Review
- Sphingolipid Metabolism and Signalling Pathways in Heart Failure: From Molecular Mechanism to Therapeutic Potential.Journal of inflammation research · 2025Review
- Mitochondria associated membranes in dilated cardiomyopathy: connecting pathogenesis and cellular dysfunction.Frontiers in cardiovascular medicine · 2025Review
- Role of bariatric surgery in improving diabetic cardiomyopathy: Molecular mechanisms and therapeutic perspectives (Review).Molecular medicine reports · 2024Review
- The diverse roles of sphingolipids in inflammatory bowel disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Review
- Ceramides are fuel gauges on the drive to cardiometabolic disease.Physiological reviews · 2024Review
- Adiponectin overexpression improves metabolic abnormalities caused by acid ceramidase deficiency but does not prolong lifespan in a mouse model of Farber Disease.Molecular genetics and metabolism reports · 2024Article
77 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Diabetic cardiomyopathy (DbCM), which consists of cardiac hypertrophy and failure in the absence of traditional risk factors, is a major contributor to increased heart failure risk in type 2 diabetes patients. In rodent models of DbCM, cardiac hypertrophy and dysfunction have been shown to depend upon saturated fatty acid (SFA) oversupply and de novo sphingolipid synthesis. However, it is not known whether these effects are mediated by bulk SFAs and sphingolipids or by individual lipid species. In this report, we demonstrate that a diet high in SFA induced cardiac hypertrophy, left ventricular systolic and diastolic dysfunction, and autophagy in mice. Furthermore, treatment with the SFA myristate, but not palmitate, induced hypertrophy and autophagy in adult primary cardiomyocytes. De novo sphingolipid synthesis was required for induction of all pathological features observed both in vitro and in vivo, and autophagy was required for induction of hypertrophy in vitro. Finally, we implicated a specific ceramide N-acyl chain length in this process and demonstrated a requirement for (dihydro)ceramide synthase 5 in cardiomyocyte autophagy and myristate-mediated hypertrophy. Thus, this report reveals a requirement for a specific sphingolipid metabolic route and dietary SFAs in the molecular pathogenesis of lipotoxic cardiomyopathy and hypertrophy.
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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.