ArticleCell death & disease2022
Adiponectin receptor agonist ameliorates cardiac lipotoxicity via enhancing ceramide metabolism in type 2 diabetic mice.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Unraveling the rationale and conducting a comprehensive assessment of AdipoRon (adiponectin receptor agonist) as a candidate drug for diabetic nephropathy and cardiomyopathy prevention and intervention-a systematic review.Naunyn-Schmiedeberg's archives of pharmacology · 2025Pooled it
- Roles of inflammation and metabolic dysfunction in cardiovascular diseases: molecular mechanisms and therapeutic targets.Molecular biomedicine · 2026Review
- Loss of Rab8a-Dependent Tethering of Lipid Droplets to Mitochondria Contributes to Hypoxia-Reoxygenation Injury.MedComm · 2026Article
- Hesperidin alleviates systemic inflammation and oxidative stress by remodeling adipose tissue lipid metabolism in periparturient dairy cows.Journal of animal science and biotechnology · 2026Article
- Enzyme-Activated Self-Assembling Peptides Mimicking Adiponectin Multimers for Nonalcoholic Fatty Liver Disease Therapy.ACS central science · 2026Article
- Integrative insights into fatty acid metabolism in diabetic cardiomyopathy: From molecular mechanisms to therapeutic strategies.iScience · 2026Review
- Assay-Dependent Variability in RBP4 and Adiponectin Quantification Affects Associations with Coronary Disease Severity and Doppler Echocardiographic Indices: A Comparative Study of Immunoturbidimetry and ELISA.International journal of general medicine · 2026Article
- Review
- Acid ceramidase as a novel target for adiponectin receptor agonist to abrogate podocyte NLRP3 inflammasome activation and glomerular inflammation during obesity.The Journal of pharmacology and experimental therapeutics · 2025Article
- Metabolomics-driven elucidation of the synergistic therapeutic mechanism of a novel SGLT-2/PPAR-γ dual receptor supramolecular system for treatment diabetes and obesity.Journal of pharmaceutical analysis · 2025Article
- The potential role of hydrogen sulfide-autophagy axis in diseases.Journal of physiology and biochemistry · 2025Review
- Circular RNA circDhx32 promotes cardiac inflammatory responses in mouse cardiac ischemia-reperfusion injury via binding to FOXO1 competed with AdipoR1.Acta pharmacologica Sinica · 2025Article
- Strengthening monocarboxylate transporters by adiponectin receptor agonist ameliorates diabetic peripheral neuropathy.Cell communication and signaling : CCS · 2025Article
- Changes in insulin, adiponectin and lipid concentrations with age are associated with frailty and reduced quality of life in dogs.Scientific reports · 2025Article
- Exercise in Diabetic Cardiomyopathy: Its Protective Effects and Molecular Mechanism.International journal of molecular sciences · 2025Review
- AdipoRon ameliorates the progression of heart failure with preserved ejection fraction via mitigating lipid accumulation and fibrosis.Journal of advanced research · 2025Article
- Oral Administration of the Adiponectin Receptor 1 Agonistic Dipeptide Tyr-Pro Prevents Hyperglycemia in Spontaneously Diabetic Torii Rats.ACS omega · 2025Article
- Adiponectin and Adiponectin Receptors in Atherosclerosis.Endocrine reviews · 2025Review
- Peroxisome proliferator‑activated receptor γ coactivator‑1α in heart disease (Review).Molecular medicine reports · 2025Review
- Sphingolipid Metabolism and Signalling Pathways in Heart Failure: From Molecular Mechanism to Therapeutic Potential.Journal of inflammation research · 2025Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulation of lipids and their metabolites induces lipotoxicity in diabetic cardiomyopathy. Lowering ceramide concentration could reduce the impact of metabolic damage to target organs. Adiponectin improves lipotoxicity through its receptors (AdiopRs), which have sequence homology with ceramidase enzymes. Therefore, cardioprotective role of AdipoR agonism by AdipoRon was investigated. Sixteen-week-old male db/m and db/db mice were fed a diet containing AdipoRon for four weeks. Phenotypic and metabolic profiles with associated cellular signaling pathways involved in lipid metabolism were investigated in the mice heart and human cardiomyocytes to establish treatment effect of AdipoRon. AdipoRon ameliorated insulin resistance, fibrosis, M1-dominant inflammation, and apoptosis in association with reduced accumulations of free fatty acid, triglycerides, and TLR4-related ceramide in the heart. This resulted in overall reduction in the level of oxidative stress which ameliorated cardiac hypertrophy and its function. AdipoRon increased the expression of AdipoR1 and AdipoR2 via pAMPK/FoxO1-induced Akt phosphorylation resulting from a decrease in PP2A level. It also increased acid ceramidase activity which reduced ceramide and increased sphingosine-1 phosphate levels in the heart of db/db mice and cultured human cardiomyocytes. Consistent upregulation of AdipoRs and their downstream regulatory pathways involving pAMPK/PPARα/PGC-1α levels led to lipid metabolism enhancement, thereby improving lipotoxicity-induced peroxisome biogenesis and oxidative stress. AdipoRon might control oxidative stress, inflammation, and apoptosis in the heart through increased AdipoR expression, acid ceramidase activity, and activation of AMPK-PPARα/PGC-1α and related downstream pathways, collectively improving cardiac lipid metabolism, hypertrophy, and functional parameters.
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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 Socratic graph.