| First Author | Davogustto GE | Year | 2021 |
| Journal | J Mol Cell Cardiol | Volume | 158 |
| Pages | 115-127 | PubMed ID | 34081952 |
| Mgi Jnum | J:306512 | Mgi Id | MGI:6715020 |
| Doi | 10.1016/j.yjmcc.2021.05.016 | Citation | Davogustto GE, et al. (2021) Metabolic remodeling precedes mTORC1-mediated cardiac hypertrophy. J Mol Cell Cardiol 158:115-127 |
| abstractText | 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 (mTORC1(iSA)) 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. |
