Metabolic remodeling precedes mTORC1-mediated cardiac hypertrophy.

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 (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.

SUBMITTER: Davogustto GE 

PROVIDER: S-EPMC8630806 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature