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ResearchIn-Press PreviewNephrology Free access | 10.1172/JCI140695

Renal tubule Cpt1a overexpression protects from kidney fibrosis by restoring mitochondrial homeostasis

Verónica Miguel,1 Jessica Tituaña,1 J. Ignacio Herrero,1 Laura Herrero,2 Dolors Serra,2 Paula Cuevas-Delgado,3 Coral Barbas,3 Diego Rodriguez-Puyol,4 Laura Marquez-Exposito,5 Marta Ruiz-Ortega,5 Carolina Castillo,6 Xin Sheng,7 Katalin Susztak,7 Miguel Ruiz-Canela,8 Jordi Salas-Salvado,9 Miguel A. Martinez-Gonzalez,8 Sagrario Ortega,11 Ricardo Ramos-Ruiz,12 and Santiago Lamas1

1Program of Physiological and Pathological Processes, Centro de Biología Molecular “Severo Ochoa", Madrid, Spain

2Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain

3Centre for Metabolomics and Bioanalysis, Universidad San Pablo-CEU, Madrid, Spain

4Department of Medicine and Medical Specialties, Alcalá University, Madrid, Spain

5Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, Fundación Jiménez Díaz-Universidad Autónoma Madrid, Madrid, Spain

6University Hospital, Alcalá de Henares, Madrid, Spain

7Division of Nephrology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

8Department of Preventive Medicine and Public Health, University of Navarra, Pampona, Spain

9Human Nutrition Unit, Faculty of Medicine and Health Sciences, Pere Virgili Health Research Institute, Rovira i Virgili University, Reus, Spain

10Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain

11Transgenics Unit, Spanish National Cancer Research Centre, Madrid, Spain

12Genomic Facility, Parque Científico de Madrid, Madrid, Spain

Find articles by Miguel, V. in: JCI | PubMed | Google Scholar

1Program of Physiological and Pathological Processes, Centro de Biología Molecular “Severo Ochoa", Madrid, Spain

2Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain

3Centre for Metabolomics and Bioanalysis, Universidad San Pablo-CEU, Madrid, Spain

4Department of Medicine and Medical Specialties, Alcalá University, Madrid, Spain

5Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, Fundación Jiménez Díaz-Universidad Autónoma Madrid, Madrid, Spain

6University Hospital, Alcalá de Henares, Madrid, Spain

7Division of Nephrology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

8Department of Preventive Medicine and Public Health, University of Navarra, Pampona, Spain

9Human Nutrition Unit, Faculty of Medicine and Health Sciences, Pere Virgili Health Research Institute, Rovira i Virgili University, Reus, Spain

10Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain

11Transgenics Unit, Spanish National Cancer Research Centre, Madrid, Spain

12Genomic Facility, Parque Científico de Madrid, Madrid, Spain

Find articles by Tituaña, J. in: JCI | PubMed | Google Scholar

1Program of Physiological and Pathological Processes, Centro de Biología Molecular “Severo Ochoa", Madrid, Spain

2Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain

3Centre for Metabolomics and Bioanalysis, Universidad San Pablo-CEU, Madrid, Spain

4Department of Medicine and Medical Specialties, Alcalá University, Madrid, Spain

5Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, Fundación Jiménez Díaz-Universidad Autónoma Madrid, Madrid, Spain

6University Hospital, Alcalá de Henares, Madrid, Spain

7Division of Nephrology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

8Department of Preventive Medicine and Public Health, University of Navarra, Pampona, Spain

9Human Nutrition Unit, Faculty of Medicine and Health Sciences, Pere Virgili Health Research Institute, Rovira i Virgili University, Reus, Spain

10Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain

11Transgenics Unit, Spanish National Cancer Research Centre, Madrid, Spain

12Genomic Facility, Parque Científico de Madrid, Madrid, Spain

Find articles by Herrero, J. in: JCI | PubMed | Google Scholar

1Program of Physiological and Pathological Processes, Centro de Biología Molecular “Severo Ochoa", Madrid, Spain

2Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain

3Centre for Metabolomics and Bioanalysis, Universidad San Pablo-CEU, Madrid, Spain

4Department of Medicine and Medical Specialties, Alcalá University, Madrid, Spain

5Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, Fundación Jiménez Díaz-Universidad Autónoma Madrid, Madrid, Spain

6University Hospital, Alcalá de Henares, Madrid, Spain

7Division of Nephrology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

8Department of Preventive Medicine and Public Health, University of Navarra, Pampona, Spain

9Human Nutrition Unit, Faculty of Medicine and Health Sciences, Pere Virgili Health Research Institute, Rovira i Virgili University, Reus, Spain

10Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain

11Transgenics Unit, Spanish National Cancer Research Centre, Madrid, Spain

12Genomic Facility, Parque Científico de Madrid, Madrid, Spain

Find articles by Herrero, L. in: JCI | PubMed | Google Scholar |

1Program of Physiological and Pathological Processes, Centro de Biología Molecular “Severo Ochoa", Madrid, Spain

2Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain

3Centre for Metabolomics and Bioanalysis, Universidad San Pablo-CEU, Madrid, Spain

4Department of Medicine and Medical Specialties, Alcalá University, Madrid, Spain

5Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, Fundación Jiménez Díaz-Universidad Autónoma Madrid, Madrid, Spain

6University Hospital, Alcalá de Henares, Madrid, Spain

7Division of Nephrology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

8Department of Preventive Medicine and Public Health, University of Navarra, Pampona, Spain

9Human Nutrition Unit, Faculty of Medicine and Health Sciences, Pere Virgili Health Research Institute, Rovira i Virgili University, Reus, Spain

10Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain

11Transgenics Unit, Spanish National Cancer Research Centre, Madrid, Spain

12Genomic Facility, Parque Científico de Madrid, Madrid, Spain

Find articles by Serra, D. in: JCI | PubMed | Google Scholar |

1Program of Physiological and Pathological Processes, Centro de Biología Molecular “Severo Ochoa", Madrid, Spain

2Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain

3Centre for Metabolomics and Bioanalysis, Universidad San Pablo-CEU, Madrid, Spain

4Department of Medicine and Medical Specialties, Alcalá University, Madrid, Spain

5Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, Fundación Jiménez Díaz-Universidad Autónoma Madrid, Madrid, Spain

6University Hospital, Alcalá de Henares, Madrid, Spain

7Division of Nephrology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

8Department of Preventive Medicine and Public Health, University of Navarra, Pampona, Spain

9Human Nutrition Unit, Faculty of Medicine and Health Sciences, Pere Virgili Health Research Institute, Rovira i Virgili University, Reus, Spain

10Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain

11Transgenics Unit, Spanish National Cancer Research Centre, Madrid, Spain

12Genomic Facility, Parque Científico de Madrid, Madrid, Spain

Find articles by Cuevas-Delgado, P. in: JCI | PubMed | Google Scholar

1Program of Physiological and Pathological Processes, Centro de Biología Molecular “Severo Ochoa", Madrid, Spain

2Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain

3Centre for Metabolomics and Bioanalysis, Universidad San Pablo-CEU, Madrid, Spain

4Department of Medicine and Medical Specialties, Alcalá University, Madrid, Spain

5Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, Fundación Jiménez Díaz-Universidad Autónoma Madrid, Madrid, Spain

6University Hospital, Alcalá de Henares, Madrid, Spain

7Division of Nephrology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

8Department of Preventive Medicine and Public Health, University of Navarra, Pampona, Spain

9Human Nutrition Unit, Faculty of Medicine and Health Sciences, Pere Virgili Health Research Institute, Rovira i Virgili University, Reus, Spain

10Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain

11Transgenics Unit, Spanish National Cancer Research Centre, Madrid, Spain

12Genomic Facility, Parque Científico de Madrid, Madrid, Spain

Find articles by Barbas, C. in: JCI | PubMed | Google Scholar |

1Program of Physiological and Pathological Processes, Centro de Biología Molecular “Severo Ochoa", Madrid, Spain

2Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain

3Centre for Metabolomics and Bioanalysis, Universidad San Pablo-CEU, Madrid, Spain

4Department of Medicine and Medical Specialties, Alcalá University, Madrid, Spain

5Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, Fundación Jiménez Díaz-Universidad Autónoma Madrid, Madrid, Spain

6University Hospital, Alcalá de Henares, Madrid, Spain

7Division of Nephrology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

8Department of Preventive Medicine and Public Health, University of Navarra, Pampona, Spain

9Human Nutrition Unit, Faculty of Medicine and Health Sciences, Pere Virgili Health Research Institute, Rovira i Virgili University, Reus, Spain

10Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain

11Transgenics Unit, Spanish National Cancer Research Centre, Madrid, Spain

12Genomic Facility, Parque Científico de Madrid, Madrid, Spain

Find articles by Rodriguez-Puyol, D. in: JCI | PubMed | Google Scholar

1Program of Physiological and Pathological Processes, Centro de Biología Molecular “Severo Ochoa", Madrid, Spain

2Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain

3Centre for Metabolomics and Bioanalysis, Universidad San Pablo-CEU, Madrid, Spain

4Department of Medicine and Medical Specialties, Alcalá University, Madrid, Spain

5Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, Fundación Jiménez Díaz-Universidad Autónoma Madrid, Madrid, Spain

6University Hospital, Alcalá de Henares, Madrid, Spain

7Division of Nephrology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

8Department of Preventive Medicine and Public Health, University of Navarra, Pampona, Spain

9Human Nutrition Unit, Faculty of Medicine and Health Sciences, Pere Virgili Health Research Institute, Rovira i Virgili University, Reus, Spain

10Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain

11Transgenics Unit, Spanish National Cancer Research Centre, Madrid, Spain

12Genomic Facility, Parque Científico de Madrid, Madrid, Spain

Find articles by Marquez-Exposito, L. in: JCI | PubMed | Google Scholar

1Program of Physiological and Pathological Processes, Centro de Biología Molecular “Severo Ochoa", Madrid, Spain

2Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain

3Centre for Metabolomics and Bioanalysis, Universidad San Pablo-CEU, Madrid, Spain

4Department of Medicine and Medical Specialties, Alcalá University, Madrid, Spain

5Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, Fundación Jiménez Díaz-Universidad Autónoma Madrid, Madrid, Spain

6University Hospital, Alcalá de Henares, Madrid, Spain

7Division of Nephrology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

8Department of Preventive Medicine and Public Health, University of Navarra, Pampona, Spain

9Human Nutrition Unit, Faculty of Medicine and Health Sciences, Pere Virgili Health Research Institute, Rovira i Virgili University, Reus, Spain

10Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain

11Transgenics Unit, Spanish National Cancer Research Centre, Madrid, Spain

12Genomic Facility, Parque Científico de Madrid, Madrid, Spain

Find articles by Ruiz-Ortega, M. in: JCI | PubMed | Google Scholar

1Program of Physiological and Pathological Processes, Centro de Biología Molecular “Severo Ochoa", Madrid, Spain

2Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain

3Centre for Metabolomics and Bioanalysis, Universidad San Pablo-CEU, Madrid, Spain

4Department of Medicine and Medical Specialties, Alcalá University, Madrid, Spain

5Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, Fundación Jiménez Díaz-Universidad Autónoma Madrid, Madrid, Spain

6University Hospital, Alcalá de Henares, Madrid, Spain

7Division of Nephrology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

8Department of Preventive Medicine and Public Health, University of Navarra, Pampona, Spain

9Human Nutrition Unit, Faculty of Medicine and Health Sciences, Pere Virgili Health Research Institute, Rovira i Virgili University, Reus, Spain

10Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain

11Transgenics Unit, Spanish National Cancer Research Centre, Madrid, Spain

12Genomic Facility, Parque Científico de Madrid, Madrid, Spain

Find articles by Castillo, C. in: JCI | PubMed | Google Scholar

1Program of Physiological and Pathological Processes, Centro de Biología Molecular “Severo Ochoa", Madrid, Spain

2Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain

3Centre for Metabolomics and Bioanalysis, Universidad San Pablo-CEU, Madrid, Spain

4Department of Medicine and Medical Specialties, Alcalá University, Madrid, Spain

5Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, Fundación Jiménez Díaz-Universidad Autónoma Madrid, Madrid, Spain

6University Hospital, Alcalá de Henares, Madrid, Spain

7Division of Nephrology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

8Department of Preventive Medicine and Public Health, University of Navarra, Pampona, Spain

9Human Nutrition Unit, Faculty of Medicine and Health Sciences, Pere Virgili Health Research Institute, Rovira i Virgili University, Reus, Spain

10Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain

11Transgenics Unit, Spanish National Cancer Research Centre, Madrid, Spain

12Genomic Facility, Parque Científico de Madrid, Madrid, Spain

Find articles by Sheng, X. in: JCI | PubMed | Google Scholar |

1Program of Physiological and Pathological Processes, Centro de Biología Molecular “Severo Ochoa", Madrid, Spain

2Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain

3Centre for Metabolomics and Bioanalysis, Universidad San Pablo-CEU, Madrid, Spain

4Department of Medicine and Medical Specialties, Alcalá University, Madrid, Spain

5Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, Fundación Jiménez Díaz-Universidad Autónoma Madrid, Madrid, Spain

6University Hospital, Alcalá de Henares, Madrid, Spain

7Division of Nephrology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

8Department of Preventive Medicine and Public Health, University of Navarra, Pampona, Spain

9Human Nutrition Unit, Faculty of Medicine and Health Sciences, Pere Virgili Health Research Institute, Rovira i Virgili University, Reus, Spain

10Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain

11Transgenics Unit, Spanish National Cancer Research Centre, Madrid, Spain

12Genomic Facility, Parque Científico de Madrid, Madrid, Spain

Find articles by Susztak, K. in: JCI | PubMed | Google Scholar |

1Program of Physiological and Pathological Processes, Centro de Biología Molecular “Severo Ochoa", Madrid, Spain

2Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain

3Centre for Metabolomics and Bioanalysis, Universidad San Pablo-CEU, Madrid, Spain

4Department of Medicine and Medical Specialties, Alcalá University, Madrid, Spain

5Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, Fundación Jiménez Díaz-Universidad Autónoma Madrid, Madrid, Spain

6University Hospital, Alcalá de Henares, Madrid, Spain

7Division of Nephrology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

8Department of Preventive Medicine and Public Health, University of Navarra, Pampona, Spain

9Human Nutrition Unit, Faculty of Medicine and Health Sciences, Pere Virgili Health Research Institute, Rovira i Virgili University, Reus, Spain

10Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain

11Transgenics Unit, Spanish National Cancer Research Centre, Madrid, Spain

12Genomic Facility, Parque Científico de Madrid, Madrid, Spain

Find articles by Ruiz-Canela, M. in: JCI | PubMed | Google Scholar |

1Program of Physiological and Pathological Processes, Centro de Biología Molecular “Severo Ochoa", Madrid, Spain

2Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain

3Centre for Metabolomics and Bioanalysis, Universidad San Pablo-CEU, Madrid, Spain

4Department of Medicine and Medical Specialties, Alcalá University, Madrid, Spain

5Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, Fundación Jiménez Díaz-Universidad Autónoma Madrid, Madrid, Spain

6University Hospital, Alcalá de Henares, Madrid, Spain

7Division of Nephrology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

8Department of Preventive Medicine and Public Health, University of Navarra, Pampona, Spain

9Human Nutrition Unit, Faculty of Medicine and Health Sciences, Pere Virgili Health Research Institute, Rovira i Virgili University, Reus, Spain

10Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain

11Transgenics Unit, Spanish National Cancer Research Centre, Madrid, Spain

12Genomic Facility, Parque Científico de Madrid, Madrid, Spain

Find articles by Salas-Salvado, J. in: JCI | PubMed | Google Scholar |

1Program of Physiological and Pathological Processes, Centro de Biología Molecular “Severo Ochoa", Madrid, Spain

2Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain

3Centre for Metabolomics and Bioanalysis, Universidad San Pablo-CEU, Madrid, Spain

4Department of Medicine and Medical Specialties, Alcalá University, Madrid, Spain

5Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, Fundación Jiménez Díaz-Universidad Autónoma Madrid, Madrid, Spain

6University Hospital, Alcalá de Henares, Madrid, Spain

7Division of Nephrology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

8Department of Preventive Medicine and Public Health, University of Navarra, Pampona, Spain

9Human Nutrition Unit, Faculty of Medicine and Health Sciences, Pere Virgili Health Research Institute, Rovira i Virgili University, Reus, Spain

10Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain

11Transgenics Unit, Spanish National Cancer Research Centre, Madrid, Spain

12Genomic Facility, Parque Científico de Madrid, Madrid, Spain

Find articles by Martinez-Gonzalez, M. in: JCI | PubMed | Google Scholar |

1Program of Physiological and Pathological Processes, Centro de Biología Molecular “Severo Ochoa", Madrid, Spain

2Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain

3Centre for Metabolomics and Bioanalysis, Universidad San Pablo-CEU, Madrid, Spain

4Department of Medicine and Medical Specialties, Alcalá University, Madrid, Spain

5Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, Fundación Jiménez Díaz-Universidad Autónoma Madrid, Madrid, Spain

6University Hospital, Alcalá de Henares, Madrid, Spain

7Division of Nephrology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

8Department of Preventive Medicine and Public Health, University of Navarra, Pampona, Spain

9Human Nutrition Unit, Faculty of Medicine and Health Sciences, Pere Virgili Health Research Institute, Rovira i Virgili University, Reus, Spain

10Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain

11Transgenics Unit, Spanish National Cancer Research Centre, Madrid, Spain

12Genomic Facility, Parque Científico de Madrid, Madrid, Spain

Find articles by Ortega, S. in: JCI | PubMed | Google Scholar |

1Program of Physiological and Pathological Processes, Centro de Biología Molecular “Severo Ochoa", Madrid, Spain

2Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain

3Centre for Metabolomics and Bioanalysis, Universidad San Pablo-CEU, Madrid, Spain

4Department of Medicine and Medical Specialties, Alcalá University, Madrid, Spain

5Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, Fundación Jiménez Díaz-Universidad Autónoma Madrid, Madrid, Spain

6University Hospital, Alcalá de Henares, Madrid, Spain

7Division of Nephrology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

8Department of Preventive Medicine and Public Health, University of Navarra, Pampona, Spain

9Human Nutrition Unit, Faculty of Medicine and Health Sciences, Pere Virgili Health Research Institute, Rovira i Virgili University, Reus, Spain

10Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain

11Transgenics Unit, Spanish National Cancer Research Centre, Madrid, Spain

12Genomic Facility, Parque Científico de Madrid, Madrid, Spain

Find articles by Ramos-Ruiz, R. in: JCI | PubMed | Google Scholar

1Program of Physiological and Pathological Processes, Centro de Biología Molecular “Severo Ochoa", Madrid, Spain

2Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain

3Centre for Metabolomics and Bioanalysis, Universidad San Pablo-CEU, Madrid, Spain

4Department of Medicine and Medical Specialties, Alcalá University, Madrid, Spain

5Cellular and Molecular Biology in Renal and Vascular Pathology Laboratory, Fundación Jiménez Díaz-Universidad Autónoma Madrid, Madrid, Spain

6University Hospital, Alcalá de Henares, Madrid, Spain

7Division of Nephrology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States of America

8Department of Preventive Medicine and Public Health, University of Navarra, Pampona, Spain

9Human Nutrition Unit, Faculty of Medicine and Health Sciences, Pere Virgili Health Research Institute, Rovira i Virgili University, Reus, Spain

10Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain

11Transgenics Unit, Spanish National Cancer Research Centre, Madrid, Spain

12Genomic Facility, Parque Científico de Madrid, Madrid, Spain

Find articles by Lamas, S. in: JCI | PubMed | Google Scholar |

Published January 19, 2021 - More info

J Clin Invest. https://doi.org/10.1172/JCI140695.
Copyright © 2021, American Society for Clinical Investigation
Published January 19, 2021 - Version history
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Abstract

Chronic kidney disease (CKD) remains a major epidemiological, clinical and biomedical challenge. During CKD, renal tubular epithelial cells (TECs) suffer a persistent inflammatory and profibrotic response. Fatty acid oxidation (FAO), the main source of energy for TECs, is reduced in kidney fibrosis and contributes to its pathogenesis. To determine if FAO gain-of-function (FAO-GOF) could protect from fibrosis, we generated a conditional transgenic mouse model with overexpression of the fatty acid shuttling enzyme carnitine palmitoyl-transferase 1 A (CPT1A) in TECs. Cpt1a knock-in mice subjected to three different models of renal fibrosis (unilateral ureteral obstruction, folic acid nephropathy-FAN and adenine induced nephrotoxicity) exhibited decreased expression of fibrotic markers, a blunted pro-inflammatory response and reduced epithelial cell damage and macrophage influx. Protection from fibrosis was also observed when Cpt1a overexpression was induced after FAN. FAO-GOF restituted oxidative metabolism and mitochondrial number and enhanced bioenergetics increasing palmitate oxidation and ATP levels, changes also recapitulated in TECs exposed to profibrotic stimuli. Studies in patients evidenced decreased CPT1 levels and increased accumulation of short and middle chain acyl-carnitines, reflecting impaired FAO in human CKD. We propose that strategies based on FAO-GOF may constitute powerful alternatives to combat fibrosis inherent to CKD.

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