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

Verónica Miguel; Jessica Tituaña; J. Ignacio Herrero; Laura Herrero; Dolors Serra; Paula Cuevas-Delgado; Coral Barbas; Diego Rodriguez-Puyol; Laura Marquez-Exposito; Marta Ruiz-Ortega; Carolina Castillo; Xin Sheng; Katalin Susztak; Miguel Ruiz-Canela; Jordi Salas-Salvado; Miguel A. Martinez-Gonzalez; Sagrario Ortega; Ricardo Ramos-Ruiz; Santiago Lamas

doi:10.1172/JCI140695

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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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 |

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.

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

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

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