L-Carnitine Stimulates In Vivo Carbohydrate Metabolism in the Type 1 Diabetic Heart as Demonstrated by Hyperpolarized MRI
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...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-03-01
|
| Series: | Metabolites |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-1989/11/3/191 |
| _version_ | 1797540309473689600 |
|---|---|
| author | Dragana Savic Vicky Ball M. Kate Curtis Maria da Luz Sousa Fialho Kerstin N. Timm David Hauton James West Julian Griffin Lisa C. Heather Damian J. Tyler |
| author_facet | Dragana Savic Vicky Ball M. Kate Curtis Maria da Luz Sousa Fialho Kerstin N. Timm David Hauton James West Julian Griffin Lisa C. Heather Damian J. Tyler |
| author_sort | Dragana Savic |
| collection | DOAJ |
| description | 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-<sup>13</sup>C]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. |
| first_indexed | 2024-03-10T12:59:12Z |
| format | Article |
| id | doaj.art-a7f4d5ce168d412992eaac0eaedd17f7 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-10T12:59:12Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-a7f4d5ce168d412992eaac0eaedd17f72023-11-21T11:41:00ZengMDPI AGMetabolites2218-19892021-03-0111319110.3390/metabo11030191L-Carnitine Stimulates In Vivo Carbohydrate Metabolism in the Type 1 Diabetic Heart as Demonstrated by Hyperpolarized MRIDragana Savic0Vicky Ball1M. Kate Curtis2Maria da Luz Sousa Fialho3Kerstin N. Timm4David Hauton5James West6Julian Griffin7Lisa C. Heather8Damian J. Tyler9Cardiac Metabolism Research Group, Department of Physiology Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UKCardiac Metabolism Research Group, Department of Physiology Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UKCardiac Metabolism Research Group, Department of Physiology Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UKCardiac Metabolism Research Group, Department of Physiology Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UKCardiac Metabolism Research Group, Department of Physiology Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UKCardiac Metabolism Research Group, Department of Physiology Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UKDepartment of Medicine, University of Cambridge, Cambridge CB2 1TN, UKDepartment of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London SW7 2AZ, UKCardiac Metabolism Research Group, Department of Physiology Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UKCardiac Metabolism Research Group, Department of Physiology Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UKThe 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-<sup>13</sup>C]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.https://www.mdpi.com/2218-1989/11/3/191magnetic resonanceL-carnitinemetabolic imagingin vivo metabolismhyperpolarized <sup>13</sup>CLangendorff perfusion |
| spellingShingle | Dragana Savic Vicky Ball M. Kate Curtis Maria da Luz Sousa Fialho Kerstin N. Timm David Hauton James West Julian Griffin Lisa C. Heather Damian J. Tyler L-Carnitine Stimulates In Vivo Carbohydrate Metabolism in the Type 1 Diabetic Heart as Demonstrated by Hyperpolarized MRI Metabolites magnetic resonance L-carnitine metabolic imaging in vivo metabolism hyperpolarized <sup>13</sup>C Langendorff perfusion |
| title | L-Carnitine Stimulates In Vivo Carbohydrate Metabolism in the Type 1 Diabetic Heart as Demonstrated by Hyperpolarized MRI |
| title_full | L-Carnitine Stimulates In Vivo Carbohydrate Metabolism in the Type 1 Diabetic Heart as Demonstrated by Hyperpolarized MRI |
| title_fullStr | L-Carnitine Stimulates In Vivo Carbohydrate Metabolism in the Type 1 Diabetic Heart as Demonstrated by Hyperpolarized MRI |
| title_full_unstemmed | L-Carnitine Stimulates In Vivo Carbohydrate Metabolism in the Type 1 Diabetic Heart as Demonstrated by Hyperpolarized MRI |
| title_short | L-Carnitine Stimulates In Vivo Carbohydrate Metabolism in the Type 1 Diabetic Heart as Demonstrated by Hyperpolarized MRI |
| title_sort | l carnitine stimulates in vivo carbohydrate metabolism in the type 1 diabetic heart as demonstrated by hyperpolarized mri |
| topic | magnetic resonance L-carnitine metabolic imaging in vivo metabolism hyperpolarized <sup>13</sup>C Langendorff perfusion |
| url | https://www.mdpi.com/2218-1989/11/3/191 |
| work_keys_str_mv | AT draganasavic lcarnitinestimulatesinvivocarbohydratemetabolisminthetype1diabeticheartasdemonstratedbyhyperpolarizedmri AT vickyball lcarnitinestimulatesinvivocarbohydratemetabolisminthetype1diabeticheartasdemonstratedbyhyperpolarizedmri AT mkatecurtis lcarnitinestimulatesinvivocarbohydratemetabolisminthetype1diabeticheartasdemonstratedbyhyperpolarizedmri AT mariadaluzsousafialho lcarnitinestimulatesinvivocarbohydratemetabolisminthetype1diabeticheartasdemonstratedbyhyperpolarizedmri AT kerstinntimm lcarnitinestimulatesinvivocarbohydratemetabolisminthetype1diabeticheartasdemonstratedbyhyperpolarizedmri AT davidhauton lcarnitinestimulatesinvivocarbohydratemetabolisminthetype1diabeticheartasdemonstratedbyhyperpolarizedmri AT jameswest lcarnitinestimulatesinvivocarbohydratemetabolisminthetype1diabeticheartasdemonstratedbyhyperpolarizedmri AT juliangriffin lcarnitinestimulatesinvivocarbohydratemetabolisminthetype1diabeticheartasdemonstratedbyhyperpolarizedmri AT lisacheather lcarnitinestimulatesinvivocarbohydratemetabolisminthetype1diabeticheartasdemonstratedbyhyperpolarizedmri AT damianjtyler lcarnitinestimulatesinvivocarbohydratemetabolisminthetype1diabeticheartasdemonstratedbyhyperpolarizedmri |