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Article

L-Carnitine Stimulates In Vivo Carbohydrate Metabolism in the Type 1 Diabetic Heart as Demonstrated by Hyperpolarized MRI

1
Cardiac Metabolism Research Group, Department of Physiology Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK
2
Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX1 3PT, UK
3
Department of Pharmacology, University of Oxford, Oxford OX1 3PT, UK
4
Metabolomics Research Group, Department of Chemistry, University of Oxford, Oxford OX1 3PT, UK
5
Department of Medicine, University of Cambridge, Cambridge CB2 1TN, UK
6
Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London SW7 2AZ, UK
*
Author to whom correspondence should be addressed.
Academic Editors: Andre F. Martins and Myriam M. Chaumeil
Metabolites 2021, 11(3), 191; https://doi.org/10.3390/metabo11030191
Received: 27 January 2021 / Revised: 15 March 2021 / Accepted: 19 March 2021 / Published: 23 March 2021
The diabetic heart is energetically and metabolically abnormal, with increased fatty acid oxidation and decreased glucose oxidation. One factor contributing to the metabolic dysfunction in diabetes may be abnormal handling of acetyl and acyl groups by the mitochondria. L-carnitine is responsible for their transfer across the mitochondrial membrane, therefore, supplementation with L-carnitine may provide a route to improve the metabolic state of the diabetic heart. The primary aim of this study was to use hyperpolarized magnetic resonance imaging (MRI) to investigate the effects of L-carnitine supplementation on the in vivo metabolism of [1-13C]pyruvate in diabetes. Male Wistar rats were injected with either vehicle or streptozotocin (55 mg/kg) to induce type-1 diabetes. Three weeks of daily i.p. treatment with either saline or L-carnitine (3 g/kg/day) was subsequently undertaken. In vivo cardiac function and metabolism were assessed with CINE and hyperpolarized MRI, respectively. L-carnitine supplementation prevented the progression of hyperglycemia, which was observed in untreated streptozotocin injected animals and led to reductions in plasma triglyceride and ß-hydroxybutyrate concentrations. Hyperpolarized MRI revealed that L-carnitine treatment elevated pyruvate dehydrogenase flux by 3-fold in the diabetic animals, potentially through increased buffering of excess acetyl-CoA units in the mitochondria. Improved functional recovery following ischemia was also observed in the L-carnitine treated diabetic animals. View Full-Text
Keywords: magnetic resonance; L-carnitine; metabolic imaging; in vivo metabolism; hyperpolarized 13C; Langendorff perfusion; metabolomics; type-1 diabetes; cardiac imaging; streptozotocin magnetic resonance; L-carnitine; metabolic imaging; in vivo metabolism; hyperpolarized 13C; Langendorff perfusion; metabolomics; type-1 diabetes; cardiac imaging; streptozotocin
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MDPI and ACS Style

Savic, D.; Ball, V.; Curtis, M.K.; Sousa Fialho, M.d.L.; Timm, K.N.; Hauton, D.; West, J.; Griffin, J.; Heather, L.C.; Tyler, D.J. L-Carnitine Stimulates In Vivo Carbohydrate Metabolism in the Type 1 Diabetic Heart as Demonstrated by Hyperpolarized MRI. Metabolites 2021, 11, 191. https://doi.org/10.3390/metabo11030191

AMA Style

Savic D, Ball V, Curtis MK, Sousa Fialho MdL, Timm KN, Hauton D, West J, Griffin J, Heather LC, Tyler DJ. L-Carnitine Stimulates In Vivo Carbohydrate Metabolism in the Type 1 Diabetic Heart as Demonstrated by Hyperpolarized MRI. Metabolites. 2021; 11(3):191. https://doi.org/10.3390/metabo11030191

Chicago/Turabian Style

Savic, Dragana, Vicky Ball, M. K. Curtis, Maria d.L. Sousa Fialho, Kerstin N. Timm, David Hauton, James West, Julian Griffin, Lisa C. Heather, and Damian J. Tyler 2021. "L-Carnitine Stimulates In Vivo Carbohydrate Metabolism in the Type 1 Diabetic Heart as Demonstrated by Hyperpolarized MRI" Metabolites 11, no. 3: 191. https://doi.org/10.3390/metabo11030191

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