Skeletal Muscle mTORC1 Activation Increases Energy Expenditure and Reduces Longevity in Mice

摘要: The mechanistic target of rapamycin (mTORC1) is a nutrient responsive protein kinase complex that helps co-ordinate anabolic processes across all tissues. There evidence signaling through mTORC1 in skeletal muscle may be determinant energy expenditure and aging therefore components downstream potential targets for treating obesity age-associated metabolic disease. Here, we generated mice with Ckmm-Cre driven ablation Tsc1, which confers constitutive activation performed unbiased transcriptional analyses to identify pathways candidate genes explain how activity regulates balance aging. Activation produced striking resistance diet- age-induced without inducing systemic insulin resistance. We found increases following high fat diet were mTORC1-dependent elevated caused by Tsc1 coincided the upregulation muscle-specific thermogenic mechanisms involve sarcolipin-driven futile cycling Ca2+ SERCA2. Additionally, report reduces lifespan. These findings support hypothesis its targets, specifically muscle, play role nutrient-dependent thermogenesis