ArticleBritish journal of pharmacology2015
Inhibition of L-carnitine biosynthesis and transport by methyl-γ-butyrobetaine decreases fatty acid oxidation and protects against myocardial infarction.
Article in British journal of pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 42 citations in OpenAlex.
- Microbiome-associated metabolites, valerobetaine and homocarnitine, inhibit carnitine transport via OCTN2.American journal of physiology. Cell physiology · 2026Article
- PPARα: Linking Cardiac Metabolism to Therapeutic Opportunities in Cardiovascular Diseases.Cells · 2026Review
- Distinct immunometabolic signatures of type 1 versus type 2 diabetes in a murine model of myocardial infarction.Cardiovascular diabetology · 2026Article
- Emerging therapy strategies for energy metabolism in acute myocardial infarction.Journal of translational medicine · 2025Review
- Diagnosis of deep vein thrombosis from γ-butylbetaine and L-carnitine in plasma and urine based on untargeted and targeted metabolomics.Scientific reports · 2025Article
- Comprehensive review of the expanding roles of the carnitine pool in metabolic physiology: beyond fatty acid oxidation.Journal of translational medicine · 2025Review
- Cardioprotective strategies in myocardial ischemia-reperfusion injury: Implications for improving clinical translation.Journal of molecular and cellular cardiology plus · 2025Review
- Mitochondria and myocardial ischemia/reperfusion injury: Effects of Chinese herbal medicine and the underlying mechanisms.Journal of pharmaceutical analysis · 2025Review
- Knockout of Tmlhe in mice is not associated with autism spectrum disorder phenotypes or motor dysfunction despite low carnitine levels.Molecular autism · 2023Article
- Data on cardiac and vascular functionality inData in brief · 2023Article
- Binding versus Enzymatic Processing of ε-Trimethyllysine Dioxygenase Substrate Analogues.ACS medicinal chemistry letters · 2022Article
- Mildronate triggers growth suppression and lipid accumulation in largemouth bass (Micropterus salmoides) through disturbing lipid metabolism.Fish physiology and biochemistry · 2022Article
- Protective Effects of Meldonium in Experimental Models of Cardiovascular Complications with a Potential Application in COVID-19.International journal of molecular sciences · 2021Article
- Cardiometabolism as an Interlocking Puzzle between the Healthy and Diseased Heart: New Frontiers in Therapeutic Applications.Journal of clinical medicine · 2021Review
- Inhibition of Fatty Acid Metabolism Increases EPA and DHA Levels and Protects against Myocardial Ischaemia-Reperfusion Injury in Zucker Rats.Oxidative medicine and cellular longevity · 2021Article
- Mitochondrial Metabolism in Myocardial Remodeling and Mechanical Unloading: Implications for Ischemic Heart Disease.Frontiers in cardiovascular medicine · 2021Review
- Cardiac metabolism as a driver and therapeutic target of myocardial infarction.Journal of cellular and molecular medicine · 2020Review
- Whole grain intake associated molecule 5-aminovaleric acid betaine decreases β-oxidation of fatty acids in mouse cardiomyocytes.Scientific reports · 2018Article
- Recent examples of α-ketoglutarate-dependent mononuclear non-haem iron enzymes in natural product biosyntheses.Natural product reports · 2018Review
- Crystal structures of binary compounds of meldonium 3-(1,1,1-tri-methyl-hydrazin-1-ium-2-yl)prop-ano-ate with sodium bromide and sodium iodide.Acta crystallographica. Section E, Crystallographic communications · 2018Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThe important pathological consequences of ischaemic heart disease arise from the detrimental effects of the accumulation of long-chain acylcarnitines in the case of acute ischaemia-reperfusion. The aim of this study is to test whether decreasing the L-carnitine content represents an effective strategy to decrease accumulation of long-chain acylcarnitines and to reduce fatty acid oxidation in order to protect the heart against acute ischaemia-reperfusion injury. KEY
resultsIn this study, we used a novel compound, 4-[ethyl(dimethyl)ammonio]butanoate (Methyl-GBB), which inhibits γ-butyrobetaine dioxygenase (IC₅₀ 3 μM) and organic cation transporter 2 (OCTN2, IC₅₀ 3 μM), and, in turn, decreases levels of L-carnitine and acylcarnitines in heart tissue. Methyl-GBB reduced both mitochondrial and peroxisomal palmitate oxidation rates by 44 and 53% respectively. In isolated hearts treated with Methyl-GBB, uptake and oxidation rates of labelled palmitate were decreased by 40%, while glucose oxidation was increased twofold. Methyl-GBB (5 or 20 mg·kg(-1)) decreased the infarct size by 45-48%. In vivo pretreatment with Methyl-GBB (20 mg·kg(-1)) attenuated the infarct size by 45% and improved 24 h survival of rats by 20-30%. CONCLUSIONS AND IMPLICATIONS: Reduction of L-carnitine and long-chain acylcarnitine content by the inhibition of OCTN2 represents an effective strategy to protect the heart against ischaemia-reperfusion-induced damage. Methyl-GBB treatment exerted cardioprotective effects and increased survival by limiting long-chain fatty acid oxidation and facilitating glucose metabolism.
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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.