ArticleNature2017
Structural insights into adiponectin receptors suggest ceramidase activity.
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 136 papers.
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Who cites it
136 citing papers in PubMed, 210 citations in OpenAlex.
- 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
- Machine learning reveals serum sphingolipids as cholesterol-independent biomarkers of coronary artery disease.The Journal of clinical investigation · 2020Trial
- 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
- Identification of alpha1-oleate as a potent regulator of adipokine-dependent metabolism, in bladder cancer tissue.Cancer & metabolism · 2026Article
- Adiponectin exerts sex-dependent effects on lipid, amino acid, and glucose metabolism during caloric restriction.PLoS biology · 2026Article
- Adiponectin and aging: Mechanistic insights, clinical paradox, and therapeutic horizons.Ageing research reviews · 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
- Article
- Crosstalk Between Leptin and Adiponectin in Colorectal Cancer: Molecular Mechanisms and Oncogenic Pathways.International journal of molecular sciences · 2026Review
- Lipidomic Analysis of Plasma Extracellular Vesicles from Adiponectin Deficient Mice or Metabolic Syndrome Patients Reveals Pro-Oxidative and Pro-Inflammatory Lipid Signatures Correlating with Metabolic Dysfunction.Journal of extracellular vesicles · 2026Article
- Adipose tissue ceramides: emerging lipid components of extracellular vesicles and their influence on metabolic dysregulation.Frontiers in endocrinology · 2026Review
- Electron microscopy reveals saturated fatty acid-induced membrane defects in AdipoR2-depleted cells.Lipids in health and disease · 2025Article
- Parallel Pathways, Divergent Outcomes: Adipose Tissue-Neural Crosstalk in Depression and Obesity.Journal of clinical medicine · 2025Review
- Single-Cell Transcriptomics in Inherited Retinal Dystrophies: Current Findings and Emerging Perspectives.Genes · 2025Review
- Adiponectin and gastric fundus: A potential target for gut-brain axis dysfunctions.Physiological reports · 2025Review
- An inducible and reversible system to regulate unsaturated fatty acid biosynthesis in C. elegans.G3 (Bethesda, Md.) · 2025Article
- Adiponectin and Adiponectin Receptors in Atherosclerosis.Endocrine reviews · 2025Review
- Strength Training can Modulate Urinary Adipokine Levels in Healthy Young Males.International journal of exercise science · 2025Article
- The Role ofInternational journal of general medicine · 2025Article
- Selectively targeting the AdipoR2-CaM-CaMKII-NOS3 axis by SCM-198 as a rapid-acting therapy for advanced acute liver failure.Nature communications · 2024Article
76 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 6 institutions in 4 countries.
Funding
Abstract
Adiponectin receptors (ADIPORs) are integral membrane proteins that control glucose and lipid metabolism by mediating, at least in part, a cellular ceramidase activity that catalyses the hydrolysis of ceramide to produce sphingosine and a free fatty acid (FFA). The crystal structures of the two receptor subtypes, ADIPOR1 and ADIPOR2, show a similar overall seven-transmembrane-domain architecture with large unoccupied cavities and a zinc binding site within the seven transmembrane domain. However, the molecular mechanisms by which ADIPORs function are not known. Here we describe the crystal structure of ADIPOR2 bound to a FFA molecule and show that ADIPOR2 possesses intrinsic basal ceramidase activity that is enhanced by adiponectin. We also identify a ceramide binding pose and propose a possible mechanism for the hydrolytic activity of ADIPOR2 using computational approaches. In molecular dynamics simulations, the side chains of residues coordinating the zinc rearrange quickly to promote the nucleophilic attack of a zinc-bound hydroxide ion onto the ceramide amide carbonyl. Furthermore, we present a revised ADIPOR1 crystal structure exhibiting a seven-transmembrane-domain architecture that is clearly distinct from that of ADIPOR2. In this structure, no FFA is observed and the ceramide binding pocket and putative zinc catalytic site are exposed to the inner membrane leaflet. ADIPOR1 also possesses intrinsic ceramidase activity, so we suspect that the two distinct structures may represent key steps in the enzymatic activity of ADIPORs. The ceramidase activity is low, however, and further studies will be required to characterize fully the enzymatic parameters and substrate specificity of ADIPORs. These insights into ADIPOR function will enable the structure-based design of potent modulators of these clinically relevant enzymes.
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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 OpenQuestion graph.