HIF-1α and PPARγ during physiological cardiac hypertrophy induced by pregnancy: Transcriptional activities and effects on target genes.
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.
Universidad de Sonora, Departamento de Ciencias Químico Biológicas y Agropecuarias, Universidad de Sonora Unidad Regional Sur, Apartado Postal 85390, Navojoa, Sonora, Mexico. Electronic address: jorganis@navojoa.uson.mx.
José G
JG
Soñanez-Organis
Universidad de Sonora, Departamento de Ciencias Químico Biológicas y Agropecuarias, Universidad de Sonora Unidad Regional Sur, Apartado Postal 85390, Navojoa, Sonora, Mexico.
José A
JA
Godoy-Lugo
Universidad de Sonora, Departamento de Ciencias Químico Biológicas y Agropecuarias, Universidad de Sonora Unidad Regional Sur, Apartado Postal 85390, Navojoa, Sonora, Mexico.
Magally L E
ML
Hernández-Palomares
Universidad de Sonora, Departamento de Ciencias Químico Biológicas y Agropecuarias, Universidad de Sonora Unidad Regional Sur, Apartado Postal 85390, Navojoa, Sonora, Mexico.
Daniel
D
Rodríguez-Martínez
Universidad de Sonora, Departamento de Ciencias Químico Biológicas y Agropecuarias, Universidad de Sonora Unidad Regional Sur, Apartado Postal 85390, Navojoa, Sonora, Mexico.
Jesús A
JA
Rosas-Rodríguez
Universidad de Sonora, Departamento de Ciencias Químico Biológicas y Agropecuarias, Universidad de Sonora Unidad Regional Sur, Apartado Postal 85390, Navojoa, Sonora, Mexico.
Guadalupe
G
González-Ochoa
Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, A.P. 199, Colima, C.P. 28045 Colima, Mexico.
Adolfo
A
Virgen-Ortiz
School of Natural Sciences, University of California Merced, 5200 N Lake Road, Merced, CA 95343, USA.
Rudy M
RM
Ortiz
D000818:Animals; D002320:Cardiovascular Physiological Phenomena / Q000235:genetics*; D005260:Female; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D050536:Glycerol-3-Phosphate Dehydrogenase (NAD+) / Q000378:metabolism; D006352:Heart Ventricles / Q000201:enzymology / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D009929:Organ Size; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D012333:RNA, Messenger; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic
C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D047495:PPAR gamma; C000613696:PPAR gamma, rat; D012333:RNA, Messenger; D050536:Glycerol-3-Phosphate Dehydrogenase (NAD+); D005987:Glyceraldehyde-3-Phosphate Dehydrogenases
Glycerol; Glycolysis; Lipids; Metabolism; Postpartum