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
Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/
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
Article's DOI: 10.1016/j.yjmcc.2021.05.016
Entity: Universitat Rovira i Virgili
Journal publication year: 2021
Publication Type: Journal Publications
Repositori URV