Hepatic levels of S-adenosylmethionine regulate the adaptive response to fasting.

Autor:	Capelo-Diz A; Gene Regulatory Control in Disease Laboratory, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, A Coruña 15706, Spain., Lachiondo-Ortega S; Liver Disease Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, 48160 Derio, Spain., Fernández-Ramos D; Precision Medicine and Metabolism Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, 48160 Derio, Spain; Centro de investigación Biomedica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de salud Carlos III, 28029 Madrid, Spain., Cañas-Martín J; Gene Regulatory Control in Disease Laboratory, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, A Coruña 15706, Spain., Goikoetxea-Usandizaga N; Liver Disease Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, 48160 Derio, Spain., Serrano-Maciá M; Liver Disease Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, 48160 Derio, Spain., González-Rellan MJ; Department of Physiology, CIMUS, University of Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Santiago de Compostela, A Coruña 15706, Spain., Mosca L; Department of Precision Medicine, University of Campania 'Luigi Vanvitelli', Via Luigi De Crecchio 7, 80138 Naples, Italy., Blazquez-Vicens J; Gene Regulatory Control in Disease Laboratory, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, A Coruña 15706, Spain., Tinahones-Ruano A; Gene Regulatory Control in Disease Laboratory, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, A Coruña 15706, Spain., Fondevila MF; Department of Physiology, CIMUS, University of Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Santiago de Compostela, A Coruña 15706, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, A Coruña 15706, Spain., Buyan M; Liver Disease Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, 48160 Derio, Spain., Delgado TC; Liver Disease Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, 48160 Derio, Spain., Gutierrez de Juan V; Precision Medicine and Metabolism Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, 48160 Derio, Spain., Ayuso-García P; Gene Regulatory Control in Disease Laboratory, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, A Coruña 15706, Spain., Sánchez-Rueda A; Gene Regulatory Control in Disease Laboratory, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, A Coruña 15706, Spain., Velasco-Avilés S; Gene Regulatory Control in Disease Laboratory, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, A Coruña 15706, Spain., Fernández-Susavila H; Gene Regulatory Control in Disease Laboratory, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, A Coruña 15706, Spain., Riobello-Suárez C; Gene Regulatory Control in Disease Laboratory, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, A Coruña 15706, Spain., Dziechciarz B; Gene Regulatory Control in Disease Laboratory, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, A Coruña 15706, Spain., Montiel-Duarte C; The John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham NG11 8NS, UK., Lopitz-Otsoa F; Precision Medicine and Metabolism Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, 48160 Derio, Spain., Bizkarguenaga M; Precision Medicine and Metabolism Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, 48160 Derio, Spain., Bilbao-García J; Precision Medicine and Metabolism Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, 48160 Derio, Spain., Bernardo-Seisdedos G; Precision Medicine and Metabolism Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, 48160 Derio, Spain., Senra A; CIMUS, University of Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Santiago de Compostela, A Coruña 15706, Spain., Soriano-Navarro M; Electron Microscopy Core Facility, Centro de Investigación Príncipe Felipe (CIPF), Valencia 46012, Spain., Millet O; Precision Medicine and Metabolism Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, 48160 Derio, Spain., Díaz-Lagares Á; Epigenomics Unit, Cancer Epigenomics, Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago de Compostela (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), Santiago de Compostela, A Coruña 15706, Spain., Crujeiras AB; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, A Coruña 15706, Spain; Epigenomics in Endocrinology and Nutrition Group, Epigenomics Unit, Instituto de Investigacion Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago de Compostela (CHUS/SERGAS), 15706 Santiago de Compostela, Spain., Bao-Caamano A; Epigenomics in Endocrinology and Nutrition Group, Epigenomics Unit, Instituto de Investigacion Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago de Compostela (CHUS/SERGAS), 15706 Santiago de Compostela, Spain., Cabrera D; Metabolomics Platform, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, 48160 Derio, Spain., van Liempd S; Metabolomics Platform, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, 48160 Derio, Spain., Tamayo-Carro M; Nerve Disorders Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, 48160 Derio, Spain., Borzacchiello L; Department of Precision Medicine, University of Campania 'Luigi Vanvitelli', Via Luigi De Crecchio 7, 80138 Naples, Italy., Gomez-Santos B; Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, Leioa, Spain., Buqué X; Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, Leioa, Spain., Sáenz de Urturi D; Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, Leioa, Spain., González-Romero F; Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, Leioa, Spain., Simon J; Liver Disease Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, 48160 Derio, Spain., Rodríguez-Agudo R; Liver Disease Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, 48160 Derio, Spain., Ruiz A; Laboratory of Neurobiology, Achucarro Basque Center for Neuroscience, Department of Neurosciences, University of Basque Country (UPV/EHU), Centro de investigación Biomedica en Red de Enfermedades Neurodegenerativas (CIBERNED), 48940 Leioa, Spain., Matute C; Laboratory of Neurobiology, Achucarro Basque Center for Neuroscience, Department of Neurosciences, University of Basque Country (UPV/EHU), Centro de investigación Biomedica en Red de Enfermedades Neurodegenerativas (CIBERNED), 48940 Leioa, Spain., Beiroa D; Experimental Biomedicine Center (CEBEGA), University of Santiago de Compostela, A Coruña 15706, Spain., Falcon-Perez JM; Centro de investigación Biomedica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de salud Carlos III, 28029 Madrid, Spain; Metabolomics Platform, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, 48160 Derio, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Bizkaia 48009, Spain., Aspichueta P; Centro de investigación Biomedica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de salud Carlos III, 28029 Madrid, Spain; Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, Leioa, Spain; Biocruces Bizkaia Health Research Institute, Barakaldo, Spain., Rodríguez-Cuesta J; Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, 48160 Derio, Spain., Porcelli M; Department of Precision Medicine, University of Campania 'Luigi Vanvitelli', Via Luigi De Crecchio 7, 80138 Naples, Italy., Pajares MA; Centro de Investigaciones Biológicas Margarita Salas (CSIC), Ramiro de Maeztu 9, 28040 Madrid, Spain., Ameneiro C; Stem Cells and Human Diseases, CIMUS, University of Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Santiago de Compostela, A Coruña 15706, Spain., Fidalgo M; Stem Cells and Human Diseases, CIMUS, University of Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Santiago de Compostela, A Coruña 15706, Spain., Aransay AM; Genome Analysis Plataform, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, 48160 Derio, Spain., Lama-Díaz T; DNA Repair and Genome Integrity Laboratory, CIMUS, University of Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Santiago de Compostela, A Coruña 15706, Spain., Blanco MG; DNA Repair and Genome Integrity Laboratory, CIMUS, University of Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Santiago de Compostela, A Coruña 15706, Spain; Department of Biochemistry and Molecular Biology, University of Santiago de Compostela, Plaza do Obradoiro s/n, Santiago de Compostela, Spain., López M; Department of Physiology, CIMUS, University of Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Santiago de Compostela, A Coruña 15706, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, A Coruña 15706, Spain., Villa-Bellosta R; Department of Biochemistry and Molecular Biology, University of Santiago de Compostela, Plaza do Obradoiro s/n, Santiago de Compostela, Spain; Metabolic Homeostasis and Vascular Calcification Laboratory, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, A Coruña 15706, Spain., Müller TD; Institute for Diabetes and Obesity, Helmholtz Zentrum Munich, and German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany., Nogueiras R; Department of Physiology, CIMUS, University of Santiago de Compostela, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Santiago de Compostela, A Coruña 15706, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, A Coruña 15706, Spain; Oportunius Program, Galician Agency of Innovation (GAIN), Xunta de Galicia, Santiago de Compostela, A Coruña, Spain., Woodhoo A; Gene Regulatory Control in Disease Laboratory, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, A Coruña 15706, Spain; Nerve Disorders Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, 48160 Derio, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Bizkaia 48009, Spain; Oportunius Program, Galician Agency of Innovation (GAIN), Xunta de Galicia, Santiago de Compostela, A Coruña, Spain; Department of Functional Biology, University of Santiago de Compostela, Plaza do Obradoiro s/n, Santiago de Compostela, Spain., Martínez-Chantar ML; Liver Disease Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, 48160 Derio, Spain; Centro de investigación Biomedica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de salud Carlos III, 28029 Madrid, Spain. Electronic address: mlmartinez@cicbiogune.es., Varela-Rey M; Gene Regulatory Control in Disease Laboratory, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, A Coruña 15706, Spain; Liver Disease Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, 48160 Derio, Spain; Centro de investigación Biomedica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de salud Carlos III, 28029 Madrid, Spain; Department of Biochemistry and Molecular Biology, University of Santiago de Compostela, Plaza do Obradoiro s/n, Santiago de Compostela, Spain. Electronic address: martavarela.rey@usc.es.
Jazyk:	angličtina
Zdroj:	Cell metabolism [Cell Metab] 2023 Aug 08; Vol. 35 (8), pp. 1373-1389.e8. Date of Electronic Publication: 2023 Jul 31.
DOI:	10.1016/j.cmet.2023.07.002
Abstrakt:	There has been an intense focus to uncover the molecular mechanisms by which fasting triggers the adaptive cellular responses in the major organs of the body. Here, we show that in mice, hepatic S-adenosylmethionine (SAMe)-the principal methyl donor-acts as a metabolic sensor of nutrition to fine-tune the catabolic-fasting response by modulating phosphatidylethanolamine N-methyltransferase (PEMT) activity, endoplasmic reticulum-mitochondria contacts, β-oxidation, and ATP production in the liver, together with FGF21-mediated lipolysis and thermogenesis in adipose tissues. Notably, we show that glucagon induces the expression of the hepatic SAMe-synthesizing enzyme methionine adenosyltransferase α1 (MAT1A), which translocates to mitochondria-associated membranes. This leads to the production of this metabolite at these sites, which acts as a brake to prevent excessive β-oxidation and mitochondrial ATP synthesis and thereby endoplasmic reticulum stress and liver injury. This work provides important insights into the previously undescribed function of SAMe as a new arm of the metabolic adaptation to fasting. Competing Interests: Declaration of interests M.L.M.-C. advises for Mitotherapeutix. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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