Cardiac REDD1 alters glucose and fatty acid metabolic gene expression via an mTORC1-independent, PPARα-dependent mechanism and drives hypertrophic growth

Together, our findings suggest that physiological glucose-induced and pathological pressure overload-induced REDD1 is required for enhancing glucose oxidation and suppressing fatty acid oxidation in cardiomyocytes. In this way, REDD1 supports cardiac hypertrophic growth. We also outline a mechanism whereby REDD1 inhibits PPARα activity, thereby inhibiting the expression of its target genes, including <i>PDK4</i> and those involved in fatty acid oxidation. Finally, we demonstrate that these effects are independent of REDD1's ability to inhibit mTORC1.