Divergent Transcriptional Response To Mtorc1-Mediated Nutrient Signaling In Mouse Liver And Skeletal Muscle

The mechanistic target of rapamycin complex 1 (mTORC1) has a central role in balancing nutrients and growth factors with metabolic processes. Many of its mediated processes can vary between tissues to meet specific metabolic demands. Here we examine this process in mouse liver and skeletal muscle to characterize the tissue specific transcriptional response to the mTORC1 inhibitor rapamycin. We performed RNA-seq analysis on fasted tissue over a refeeding time course with and without rapamycin. Since the canonical regulation of mTORC1 is active in response to nutrient abundance and inactive during nutrient deprivation, our goal was to capture the transcriptional elements that are regulated by mTORC1 activation in both tissues. We observed altered expression of major metabolic pathways in the liver response to rapamycin but not in skeletal muscle. In addition, our time course analysis revealed a distinct increase in expression shift duration in response to rapamycin. Together our data show a clear tissue specific transcriptional response to rapamycin and a differential expression pattern that's detection was made possible through our analysis of multiple time points.