Metabolic remodeling precedes mTORC1-mediated cardiac hypertrophy.
J Mol Cell Cardiol
; 158: 115-127, 2021 09.
Article
em En
| MEDLINE
| ID: mdl-34081952
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 ANDRESULTS:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Cardiomegalia
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Técnicas de Silenciamento de Genes
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Alvo Mecanístico do Complexo 1 de Rapamicina
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Glucose
Limite:
Animals
Idioma:
En
Revista:
J Mol Cell Cardiol
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos