Pantothenate kinase 4 controls skeletal muscle substrate metabolism
Abstract Metabolic flexibility in skeletal muscle is essential for maintaining healthy glucose and lipid metabolism, and its dysfunction is closely linked to metabolic diseases. Exercise enhances metabolic flexibility, making it an important tool for discovering mechanisms that promote metabolic hea...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55036-w |
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| author | Adriana Miranda-Cervantes Andreas M. Fritzen Steffen H. Raun Ondřej Hodek Lisbeth L. V. Møller Kornelia Johann Luisa Deisen Paul Gregorevic Anders Gudiksen Anna Artati Jerzy Adamski Nicoline R. Andersen Casper M. Sigvardsen Christian S. Carl Christian T. Voldstedlund Rasmus Kjøbsted Stefanie M. Hauck Peter Schjerling Thomas E. Jensen Alberto Cebrian-Serrano Markus Jähnert Pascal Gottmann Ingo Burtscher Heiko Lickert Henriette Pilegaard Annette Schürmann Matthias H. Tschöp Thomas Moritz Timo D. Müller Lykke Sylow Bente Kiens Erik A. Richter Maximilian Kleinert |
| author_facet | Adriana Miranda-Cervantes Andreas M. Fritzen Steffen H. Raun Ondřej Hodek Lisbeth L. V. Møller Kornelia Johann Luisa Deisen Paul Gregorevic Anders Gudiksen Anna Artati Jerzy Adamski Nicoline R. Andersen Casper M. Sigvardsen Christian S. Carl Christian T. Voldstedlund Rasmus Kjøbsted Stefanie M. Hauck Peter Schjerling Thomas E. Jensen Alberto Cebrian-Serrano Markus Jähnert Pascal Gottmann Ingo Burtscher Heiko Lickert Henriette Pilegaard Annette Schürmann Matthias H. Tschöp Thomas Moritz Timo D. Müller Lykke Sylow Bente Kiens Erik A. Richter Maximilian Kleinert |
| author_sort | Adriana Miranda-Cervantes |
| collection | DOAJ |
| description | Abstract Metabolic flexibility in skeletal muscle is essential for maintaining healthy glucose and lipid metabolism, and its dysfunction is closely linked to metabolic diseases. Exercise enhances metabolic flexibility, making it an important tool for discovering mechanisms that promote metabolic health. Here we show that pantothenate kinase 4 (PanK4) is a new conserved exercise target with high abundance in muscle. Muscle-specific deletion of PanK4 impairs fatty acid oxidation which is related to higher intramuscular acetyl-CoA and malonyl-CoA levels. Elevated acetyl-CoA levels persist regardless of feeding state and are associated with whole-body glucose intolerance, reduced insulin-stimulated glucose uptake in glycolytic muscle, and impaired glucose uptake during exercise. Conversely, increasing PanK4 levels in glycolytic muscle lowers acetyl-CoA and enhances glucose uptake. Our findings highlight PanK4 as an important regulator of acetyl-CoA levels, playing a key role in both muscle lipid and glucose metabolism. |
| format | Article |
| id | doaj-art-e19d0adab9c5437bb8c791ca4a79e2b1 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-e19d0adab9c5437bb8c791ca4a79e2b12025-01-05T12:41:09ZengNature PortfolioNature Communications2041-17232025-01-0116111510.1038/s41467-024-55036-wPantothenate kinase 4 controls skeletal muscle substrate metabolismAdriana Miranda-Cervantes0Andreas M. Fritzen1Steffen H. Raun2Ondřej Hodek3Lisbeth L. V. Møller4Kornelia Johann5Luisa Deisen6Paul Gregorevic7Anders Gudiksen8Anna Artati9Jerzy Adamski10Nicoline R. Andersen11Casper M. Sigvardsen12Christian S. Carl13Christian T. Voldstedlund14Rasmus Kjøbsted15Stefanie M. Hauck16Peter Schjerling17Thomas E. Jensen18Alberto Cebrian-Serrano19Markus Jähnert20Pascal Gottmann21Ingo Burtscher22Heiko Lickert23Henriette Pilegaard24Annette Schürmann25Matthias H. Tschöp26Thomas Moritz27Timo D. Müller28Lykke Sylow29Bente Kiens30Erik A. Richter31Maximilian Kleinert32Department of Molecular Physiology of Exercise and Nutrition, German Institute of Human Nutrition (DIfE), Potsdam-RehbrueckeAugust Krogh Section for Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of CopenhagenAugust Krogh Section for Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of CopenhagenDepartment of Forest Genetics and Plant Physiology, Swedish University of Agricultural SciencesAugust Krogh Section for Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of CopenhagenDepartment of Molecular Physiology of Exercise and Nutrition, German Institute of Human Nutrition (DIfE), Potsdam-RehbrueckeDepartment of Molecular Physiology of Exercise and Nutrition, German Institute of Human Nutrition (DIfE), Potsdam-RehbrueckeDepartment of Anatomy and Physiology, University of MelbourneSection for Cell Biology and Physiology, Department of Biology, University of CopenhagenMetabolomics and Proteomics Core, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstr. 1Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstraße 1August Krogh Section for Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of CopenhagenAugust Krogh Section for Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of CopenhagenAugust Krogh Section for Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of CopenhagenAugust Krogh Section for Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of CopenhagenAugust Krogh Section for Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of CopenhagenGerman Center for Diabetes Research (DZD)Institute of Sports Medicine Copenhagen, Department of Orthopedic Surgery, Copenhagen University Hospital - Bispebjerg-FrederiksbergAugust Krogh Section for Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of CopenhagenGerman Center for Diabetes Research (DZD)German Center for Diabetes Research (DZD)German Center for Diabetes Research (DZD)German Center for Diabetes Research (DZD)German Center for Diabetes Research (DZD)Section for Cell Biology and Physiology, Department of Biology, University of CopenhagenGerman Center for Diabetes Research (DZD)German Center for Diabetes Research (DZD)Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural SciencesGerman Center for Diabetes Research (DZD)August Krogh Section for Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of CopenhagenAugust Krogh Section for Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of CopenhagenAugust Krogh Section for Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of CopenhagenDepartment of Molecular Physiology of Exercise and Nutrition, German Institute of Human Nutrition (DIfE), Potsdam-RehbrueckeAbstract Metabolic flexibility in skeletal muscle is essential for maintaining healthy glucose and lipid metabolism, and its dysfunction is closely linked to metabolic diseases. Exercise enhances metabolic flexibility, making it an important tool for discovering mechanisms that promote metabolic health. Here we show that pantothenate kinase 4 (PanK4) is a new conserved exercise target with high abundance in muscle. Muscle-specific deletion of PanK4 impairs fatty acid oxidation which is related to higher intramuscular acetyl-CoA and malonyl-CoA levels. Elevated acetyl-CoA levels persist regardless of feeding state and are associated with whole-body glucose intolerance, reduced insulin-stimulated glucose uptake in glycolytic muscle, and impaired glucose uptake during exercise. Conversely, increasing PanK4 levels in glycolytic muscle lowers acetyl-CoA and enhances glucose uptake. Our findings highlight PanK4 as an important regulator of acetyl-CoA levels, playing a key role in both muscle lipid and glucose metabolism.https://doi.org/10.1038/s41467-024-55036-w |
| spellingShingle | Adriana Miranda-Cervantes Andreas M. Fritzen Steffen H. Raun Ondřej Hodek Lisbeth L. V. Møller Kornelia Johann Luisa Deisen Paul Gregorevic Anders Gudiksen Anna Artati Jerzy Adamski Nicoline R. Andersen Casper M. Sigvardsen Christian S. Carl Christian T. Voldstedlund Rasmus Kjøbsted Stefanie M. Hauck Peter Schjerling Thomas E. Jensen Alberto Cebrian-Serrano Markus Jähnert Pascal Gottmann Ingo Burtscher Heiko Lickert Henriette Pilegaard Annette Schürmann Matthias H. Tschöp Thomas Moritz Timo D. Müller Lykke Sylow Bente Kiens Erik A. Richter Maximilian Kleinert Pantothenate kinase 4 controls skeletal muscle substrate metabolism Nature Communications |
| title | Pantothenate kinase 4 controls skeletal muscle substrate metabolism |
| title_full | Pantothenate kinase 4 controls skeletal muscle substrate metabolism |
| title_fullStr | Pantothenate kinase 4 controls skeletal muscle substrate metabolism |
| title_full_unstemmed | Pantothenate kinase 4 controls skeletal muscle substrate metabolism |
| title_short | Pantothenate kinase 4 controls skeletal muscle substrate metabolism |
| title_sort | pantothenate kinase 4 controls skeletal muscle substrate metabolism |
| url | https://doi.org/10.1038/s41467-024-55036-w |
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