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Capelo-Diz, A.* ; Lachiondo-Ortega, S.* ; Fernández-Ramos, D.* ; Cañas-Martín, J.* ; Goikoetxea-Usandizaga, N.* ; Serrano-Maciá, M.* ; Gonzalez-Rellan, M.J.* ; Mosca, L.* ; Blazquez-Vicens, J.* ; Tinahones-Ruano, A.* ; Fondevila, M.F.* ; Buyan, M.* ; Delgado, T.C.* ; Gutierrez de Juan, V.* ; Ayuso-García, P.* ; Sánchez-Rueda, A.* ; Velasco-Avilés, S.* ; Fernández-Susavila, H.* ; Riobello-Suárez, C.* ; Dziechciarz, B.* ; Montiel-Duarte, C.* ; Lopitz-Otsoa, F.* ; Bizkarguenaga, M.* ; Bilbao-García, J.* ; Bernardo-Seisdedos, G.* ; Senra, A.* ; Soriano-Navarro, M.* ; Millet, O.* ; Díaz-Lagares, * ; Crujeiras, A.B.* ; Bao-Caamano, A.* ; Cabrera, D.* ; van Liempd, S.* ; Tamayo-Carro, M.* ; Borzacchiello, L.* ; Gomez-Santos, B.* ; Buqué, X.* ; Sáenz de Urturi, D.* ; González-Romero, F.* ; Simon, J.* ; Rodríguez-Agudo, R.* ; Ruiz, A.* ; Matute, C.* ; Beiroa, D.* ; Falcón-Pérez, J.M.* ; Aspichueta, P.* ; Rodríguez-Cuesta, J.* ; Porcelli, M.* ; Pajares, M.A.* ; Ameneiro, C.* ; Fidalgo, M.* ; Aransay, A.M.* ; Lama-Díaz, T.* ; Blanco, M.G.* ; López, M.* ; Villa-Bellosta, R.* ; Müller, T.D. ; Nogueiras, R.* ; Woodhoo, A.* ; Martínez-Chantar, M.L.* ; Varela-Rey, M.*

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

Cell Metab. 35, 1373-1389.e8 (2023)

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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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords S-adenosylmethionine ; Adipose Tissue ; Caloric Restriction ; Endoplasmic Reticulum Stress ; Fasting ; Liver ; Methionine Adenosyltransferase A1 ; Mitochondria-associated-membranes ; Phosphatidylethanolamine Methyltransferase ; β-oxidation; Mitochondria-associated Membranes; Liver-injury; Fat Mass; Methionine; Metabolism; Phosphatidylethanolamine; Expression; Mice; Phosphatidylcholine; Contacts

ISSN (print) / ISBN 1550-4131

e-ISSN 1932-7420

Journal Cell Metabolism

Quellenangaben Volume: 35, Issue: 8, Pages: 1373-1389.e8

Publisher Elsevier

Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Diabetes and Obesity (IDO)

Grants ERDF A way of making Europe
AECC Scientific Foundation
Ayudas Fundacion BBVA a equipos de investigacion cientifica
La CAIXA Foundation
Redes de Investigacion
HORIZON-TMA-MSCA-Doctoral Networks
Fundacion BBVA
Accion Estrategica Ciberehd Emergentes 2018 (ISCIII)
Gilead Sciences International Research Scholars Program in Liver Disease
MCIN/AEI
European Research Council (ERC)
Ministry of Education
Departamento de Educacion del Gobierno Vasco
El FSE invierte en tu futuro
European Union
Spanish Ministry of Universities
Fundacion Cientifica AECC
Xunta de Galicia
Xunta deGalicia (AyudasPRO-ERC)
UPV/EHU
MCI/ UE/ISCiii
ERDF A way ofmaking Europe
Ayudas para apoyar grupos de investigacion del sistema Universitario Vasco
CIBERNED
MSCA Doctoral Networks
European Community
Fundacion MutuaMadrilen