ArticleJournal of advanced research2023
Metrnl ameliorates diabetic cardiomyopathy via inactivation of cGAS/STING signaling dependent on LKB1/AMPK/ULK1-mediated autophagy.
Article in Journal of advanced research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 142 citations in OpenAlex.
- Inhibition of Dyrk1a attenuates type 1 diabetic cardiomyopathy via anti‑ferroptosis.Molecular medicine reports · 2026Article
- The cGAS-STING pathway: mechanistic basis, dual biological functions and translational therapeutic advances.Apoptosis : an international journal on programmed cell death · 2026Review
- The Role of Inflammation and Immunity in Cardiovascular Disease: Molecular Mechanisms and Therapeutic Targets.MedComm · 2026Review
- Activation of autophagy through Sirt1/AMPK/mTOR mediates the protective effects of fraxin against insulin resistance and steatosis in rats.Experimental animals · 2026Article
- Serum profile of IL-29, IL-41, and raftlin in microvascular complications of type 2 diabetes mellitus.Scientific reports · 2026Article
- From energy metabolic homeostasis to immune remodeling: the role and therapeutic potential of STING signaling in the tumor microenvironment.Cell communication and signaling : CCS · 2026Review
- Metrnl in diabetes and its complications: divergent evidence and translational prospects.Journal of translational medicine · 2026Review
- NPM3 functions as a lactyltransferase to promote necroptosis in male diabetic cardiomyopathy mice models via FASN transcription modulation.Nature communications · 2026Article
- Metrnl in health and disease: tissue-specific actions and signaling networks.Apoptosis : an international journal on programmed cell death · 2026Review
- Galangin 3-methyl ether alleviates mouse hypertrophic cardiomyopathy via targeting HDAC2 and subsequently inactivating the PI3K-AKT signaling pathway.Acta pharmacologica Sinica · 2026Article
- Cardiomyoprotective effect of Tanshinone IIA in diabetic cardiomyopathy achieved through enhancing PINK1-Parkin dependent mitophagy.Histology and histopathology · 2026Article
- Cardiomyocyte-Derived USP20 Attenuates Diabetic Cardiomyopathy by Facilitating the Degradation of STING and Mitigating STING-Mediated Inflammation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Exercise and cold exposure as dual physiological stressors in MASLD: AMPK-mediated metabolic adaptation and interorgan crosstalk.Frontiers in physiology · 2026Review
- cGAS-STING and autophagy: crosstalk, molecular mechanisms, and targeted therapy.Archives of toxicology · 2026Review
- Role of the cGAS-STING signaling pathway in diabetes mellitus and its complications: from mechanisms to therapeutics.Frontiers in pharmacology · 2026Review
- Association of Serum Meteorin-Like with OCTA Metrics in Type 2 Diabetic Nonproliferative Retinopathy: A Cross-Sectional Study.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Article
- Engeletin alleviates doxorubicin-induced cardiotoxicity via the AMPK pathway in mice.Frontiers in pharmacology · 2026Article
- cGAS-STING signaling pathway as a therapeutic target in human diseases.Chinese medical journal · 2025Review
- Beyond Leptin and Adiponectin: The Diverse Roles of Adipokines in the Myocardial Hypertrophic Process and Heart Failure and Their Potential Contribution in Obesity.International journal of molecular sciences · 2025Review
- Cirsiliol alleviates diabetic cardiomyopathy by inhibiting oxidative stress and improving energy metabolism through the PPAR-α/AMPK pathway.Scientific reports · 2025Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionMeteorin-like hormone (Metrnl) is ubiquitously expressed in skeletal muscle, heart, and adipose with beneficial roles in obesity, insulin resistance, and inflammation. Metrnl is found to protect against cardiac hypertrophy and doxorubicin-induced cardiotoxicity. However, its role in diabetic cardiomyopathy (DCM) is undefined.
objectivesWe aimed to elucidate the potential roles of Metrnl in DCM.
methodsGain- andloss-of-function experimentswere utilized to determine the roles of Metrnl in the pathological processes of DCM.
resultsWe found that plasma Metrnl levels, myocardial Metrnl protein and mRNA expressions were significantly downregulated in both streptozotocin (STZ)-induced (T1D) mice and leptin receptor deficiency (db/db) (T2D) mice. Cardiac-specific overexpression (OE) of Metrnl markedly ameliorated cardiac injury and dysfunction in both T1D and T2D mice. In sharp contrast, specific deletion of Metrnl in the heart had the opposite phenotypes. In parallel, Metrnl OE ameliorated, whereas Metrnl downregulation exacerbated high glucose (HG)-elicited hypertrophy, apoptosis and oxidative damage in primary neonatal rat cardiomyocytes. Antibody-induced blockade of Metrnl eliminated the effects of benefits of Metrnl in vitro and in vivo. Mechanistically, Metrnl activated the autophagy pathway and inhibited the cGAS/STING signaling in a LKB1/AMPK/ULK1-dependent mechanism in cardiomyocytes. Besides, Metrnl-induced ULK1 phosphorylation facilitated the dephosphorylation and mitochondrial translocation of STING where it interacted with tumor necrosis factor receptor-associated factor 2 (TRAF2), a scaffold protein and E3 ubiquitin ligase that was responsible for ubiquitination and degradation of STING, rendering cardiomyocytes sensitive to autophagy activation.
conclusionThus, Metrnl may be an attractive therapeutic target or regimen for treating DCM.
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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 Socratic graph.