Pregnancy activates HIF‐1a and PPARγ in left ventricle of rats

Abstract

Pregnancy‐induced physiologic cardiac hypertrophy with important changes in the energetic metabolism to support its contractile demands and maintain viability. HIF‐1α and PPARγ activates glycolytic and glycerol‐lipid biosynthesis genes in response to pathologic hypertrophy, respectively. Therefore, these changes increase the rate of glycolysis and glucose‐to‐lipid ratio via glycerol‐3‐phosphate (G3P) pathway. However, the contribution of HIF‐1α and PPARγ to the pregnancy‐induced hypertrophy and its reversible process (postpartum) to heart metabolism are not defined. We evaluated HIF‐1α and PPARγ transcriptional activity, and quantified their target genes, key enzymes, and metabolic intermediates of glycolysis and lipid metabolism in the left ventricle of rats before, during, and after pregnancy. HIF‐1α and PPARγ activity increased 1.2‐ and 1.6‐fold, respectively, during pregnancy, and decreased to basal levels during postpartum. Expressions of mRNA for glycolytic (HK2, PFKM and GAPDH) and glycerol‐lipid biosynthesis (GPAT and GPD1) genes increased 1.6‐ to 14‐fold during pregnancy and returned to basal levels postpartum. While the increase in GPD1 expression translated to an increase in its activity, such was not the case for GAPDH suggestive of differential, post‐translational regulation of these proteins. Glycolytic (glucose, lactate and DHAP) and lipid biosynthesis (G3P and FFA) intermediates increased with pregnancy and were maintained postpartum. Results demonstrate that pregnancy induces the expression of glycolytic and glycerol‐lipid biosynthesis genes that translates to a shift in cardiac metabolism, which is sustained, at least acutely, postpartum and is associated with the activation of HIF‐1α and PPARγ.Support or Funding InformationUniversity of California Institute for Mexico and the United States and Mexico's National Council for Science and Technology (UC MEXUS‐CONACYT) and The Integral Program for Institutional Strengthening (PIFI).