ArticleNature medicine2011
Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin.
Article in Nature medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 532 papers, 1 of them a synthesis that pooled it.
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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
532 citing papers in PubMed, 1 synthesis or guideline pooled it, 872 citations in OpenAlex.
- The effects of gut microbiome manipulation on glycemic indices in patients with non-alcoholic fatty liver disease: a comprehensive umbrella review.Nutrition & diabetes · 2024Pooled it
- Caloric restriction improves glycemic control via the adiponectin-ceramide axis in non-obese men and women: the CALERIE™ 2 randomized controlled trial.Nature communications · 2026Trial
- The β3-adrenergic receptor agonist mirabegron improves glucose homeostasis in obese humans.The Journal of clinical investigation · 2020Trial
- Machine learning reveals serum sphingolipids as cholesterol-independent biomarkers of coronary artery disease.The Journal of clinical investigation · 2020Trial
- Metabolic drivers of MASLD and MASH: from hormonal imbalance to fibrosis.Diabetologia · 2026Review
- Sphingomyelin as a key negative mediator in atrial fibrillation via lipid profiling analysis and functional identification.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2026Article
- Role of adipocytes and their derived extracellular vesicles in the progression, diagnosis and treatment of liver diseases (Review).International journal of molecular medicine · 2026Review
- Sphingolipid Metabolism in Obesity: Bidirectional Regulation and Comparative Perspectives on Plant Sphingolipids.Nutrients · 2026Review
- Association between elevated adiponectin levels and 5-year risk of clinical outcomes in patients with ischaemic stroke.Stroke and vascular neurology · 2026Observational
- Cardiac Lipid Metabolism: Cells, Metabolites, and Rhythms.Circulation research · 2026Review
- Adiponectin exerts sex-dependent effects on lipid, amino acid, and glucose metabolism during caloric restriction.PLoS biology · 2026Article
- Non-coding RNAs in lipid metabolism and their roles in atherosclerosis.Nature reviews. Cardiology · 2026Review
- Adiponectin and aging: Mechanistic insights, clinical paradox, and therapeutic horizons.Ageing research reviews · 2026Review
- Emerging Insights into the Liver-Pancreas Axis: A Central Hub in the Pathogenesis of Diabetes and Metabolic Diseases.Biomolecules · 2026Review
- Lipid homeostasis plays a critical role in inherited and acquired retinal diseases.Communications biology · 2026Review
- Hesperidin alleviates systemic inflammation and oxidative stress by remodeling adipose tissue lipid metabolism in periparturient dairy cows.Journal of animal science and biotechnology · 2026Article
- Influence of body composition on the efficacy of nivolumab plus ipilimumab for metastatic clear cell renal cell carcinoma.Journal for immunotherapy of cancer · 2026Article
- Visceral adiposity, metabolic health and aging.Nature aging · 2026Review
- Bone marrow-derived mesenchymal stem cells alleviate hepatic lipid metabolism disorders after scald injury: integrating liver transcriptome and metabolome.Stem cell research & therapy · 2026Article
- Dose-response relationships of normal blood lipid levels in metabolic and endocrine diseases: mechanistic similarities, differences, and functional insights.Frontiers in endocrinology · 2026Review
472 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 6 institutions in 3 countries.
Funding
Abstract
The adipocyte-derived secretory factor adiponectin promotes insulin sensitivity, decreases inflammation and promotes cell survival. No unifying mechanism has yet explained how adiponectin can exert such a variety of beneficial systemic effects. Here, we show that adiponectin potently stimulates a ceramidase activity associated with its two receptors, AdipoR1 and AdipoR2, and enhances ceramide catabolism and formation of its antiapoptotic metabolite--sphingosine-1-phosphate (S1P)--independently of AMP-dependent kinase (AMPK). Using models of inducible apoptosis in pancreatic beta cells and cardiomyocytes, we show that transgenic overproduction of adiponectin decreases caspase-8-mediated death, whereas genetic ablation of adiponectin enhances apoptosis in vivo through a sphingolipid-mediated pathway. Ceramidase activity is impaired in cells lacking both adiponectin receptor isoforms, leading to elevated ceramide levels and enhanced susceptibility to palmitate-induced cell death. Combined, our observations suggest a unifying mechanism of action for the beneficial systemic effects exerted by adiponectin, with sphingolipid metabolism as its core upstream signaling component.
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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.