HIF-1α and PPARγ during physiological cardiac hypertrophy induced by pregnancy: Transcriptional activities and effects on target genes

Abstract

Hypoxia inducible factor 1-α (HIF-1α) and peroxisome proliferator-activated receptor γ (PPARγ) are transcription factors that activate genes involved in cellular metabolism. Physiological cardiac hypertrophy induced by pregnancy initiates compensatory changes in metabolism. However, the contributions of HIF-1α and PPARγ to this physiological status and to its reversible, metabolic process (postpartum) in the heart are not well-defined. Therefore, the aim of the present study was to evaluate the transcriptional activities of HIF-1α and PPARγ in the left ventricle of rats before, during, and after pregnancy. Furthermore, the effects of pregnancy on target genes of glycolysis and glycerol-lipid biosynthesis, key regulatory enzymes, and metabolic intermediates were evaluated. The activities of HIF-1α and PPARγ increased 1.2- and 1.6-fold, respectively, during pregnancy, and decreased to basal levels during postpartum. Expressions of mRNA for glucose transport 1 (GLUT1), enzymes of glycolysis (HK2, PFKM, and GAPDH) and glycerol-lipid biosynthesis (GPAT and GPD1) increased 1.6- to 14-fold during pregnancy and returned to basal levels postpartum. The increase in GPD1 expression translated to an increase in its activity, but such was not the case for GAPDH suggesting that post-translational regulation of these proteins is differential during pregnancy. Glycolytic (glucose, lactate, and DHAP) and glycerol-lipid biosynthesis (G3P and FFA) intermediates increased with pregnancy and were maintained postpartum. The results demonstrate that pregnancy-induced, physiological cardiac hypertrophy activates the expression of genes involved in glycolytic and glycerol-lipid biosynthesis suggesting that the shift in cardiac metabolism is mediated by the activation of HIF-1α and PPARγ.