Articles producció científica> Medicina i Cirurgia

Metabolic remodeling precedes mTORC1-mediated cardiac hypertrophy

  • Identification data

    Identifier: imarina:9287106
    Authors:
    Davogustto GESalazar RLVasquez HGKarlstaedt ADillon WPGuthrie PHMartin JRVitrac HDe La Guardia GVela DRibas-Latre ABaumgartner CEckel-Mahan KTaegtmeyer H
    Abstract:
    Rationale: The nutrient sensing mechanistic target of rapamycin complex 1 (mTORC1) and its primary inhibitor, tuberin (TSC2), are cues for the development of cardiac hypertrophy. The phenotype of mTORC1 induced hypertrophy is unknown. Objective: To examine the impact of sustained mTORC1 activation on metabolism, function, and structure of the adult heart. Methods and results: We developed a mouse model of inducible, cardiac-specific sustained mTORC1 activation (mTORC1iSA) through deletion of Tsc2. Prior to hypertrophy, rates of glucose uptake and oxidation, as well as protein and enzymatic activity of glucose 6-phosphate isomerase (GPI) were decreased, while intracellular levels of glucose 6-phosphate (G6P) were increased. Subsequently, hypertrophy developed. Transcript levels of the fetal gene program and pathways of exercise-induced hypertrophy increased, while hypertrophy did not progress to heart failure. We therefore examined the hearts of wild-type mice subjected to voluntary physical activity and observed early changes in GPI, followed by hypertrophy. Rapamycin prevented these changes in both models. Conclusion: Activation of mTORC1 in the adult heart triggers the development of a non-specific form of hypertrophy which is preceded by changes in cardiac glucose metabolism.
  • Others:

    Author, as appears in the article.: Davogustto GE; Salazar RL; Vasquez HG; Karlstaedt A; Dillon WP; Guthrie PH; Martin JR; Vitrac H; De La Guardia G; Vela D; Ribas-Latre A; Baumgartner C; Eckel-Mahan K; Taegtmeyer H
    Department: Medicina i Cirurgia
    URV's Author/s: Ribas Latre, Aleix
    Keywords: Mtorc1 Metabolism Hypertrophy Glycolysis Exercise
    Abstract: Rationale: The nutrient sensing mechanistic target of rapamycin complex 1 (mTORC1) and its primary inhibitor, tuberin (TSC2), are cues for the development of cardiac hypertrophy. The phenotype of mTORC1 induced hypertrophy is unknown. Objective: To examine the impact of sustained mTORC1 activation on metabolism, function, and structure of the adult heart. Methods and results: We developed a mouse model of inducible, cardiac-specific sustained mTORC1 activation (mTORC1iSA) through deletion of Tsc2. Prior to hypertrophy, rates of glucose uptake and oxidation, as well as protein and enzymatic activity of glucose 6-phosphate isomerase (GPI) were decreased, while intracellular levels of glucose 6-phosphate (G6P) were increased. Subsequently, hypertrophy developed. Transcript levels of the fetal gene program and pathways of exercise-induced hypertrophy increased, while hypertrophy did not progress to heart failure. We therefore examined the hearts of wild-type mice subjected to voluntary physical activity and observed early changes in GPI, followed by hypertrophy. Rapamycin prevented these changes in both models. Conclusion: Activation of mTORC1 in the adult heart triggers the development of a non-specific form of hypertrophy which is preceded by changes in cardiac glucose metabolism.
    Thematic Areas: Química Psicología Nutrição Molecular biology Medicina veterinaria Medicina ii Medicina i General medicine Engenharias iv Educação física Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Cell biology Cardiology and cardiovascular medicine Cardiac & cardiovascular systems Biotecnología
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    Author's mail: aleix.ribas@urv.cat
    Record's date: 2023-02-19
    Papper version: info:eu-repo/semantics/acceptedVersion
    Link to the original source: https://www.jmcc-online.com/article/S0022-2828(21)00110-3/fulltext
    Papper original source: Journal Of Molecular And Cellular Cardiology. 158 115-127
    APA: Davogustto GE; Salazar RL; Vasquez HG; Karlstaedt A; Dillon WP; Guthrie PH; Martin JR; Vitrac H; De La Guardia G; Vela D; Ribas-Latre A; Baumgartner C (2021). Metabolic remodeling precedes mTORC1-mediated cardiac hypertrophy. Journal Of Molecular And Cellular Cardiology, 158(), 115-127. DOI: 10.1016/j.yjmcc.2021.05.016
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Article's DOI: 10.1016/j.yjmcc.2021.05.016
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2021
    Publication Type: Journal Publications
  • Keywords:

    Cardiac & Cardiovascular Systems,Cardiology and Cardiovascular Medicine,Cell Biology,Molecular Biology
    Mtorc1
    Metabolism
    Hypertrophy
    Glycolysis
    Exercise
    Química
    Psicología
    Nutrição
    Molecular biology
    Medicina veterinaria
    Medicina ii
    Medicina i
    General medicine
    Engenharias iv
    Educação física
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Cell biology
    Cardiology and cardiovascular medicine
    Cardiac & cardiovascular systems
    Biotecnología
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