The PPARδ Agonist GW501516 Improves Lipolytic/Lipogenic Balance through CPT1 and PEPCK during the Development of Pre-Implantation Bovine Embryos

Int J Mol Sci. 2019 Dec 2;20(23):6066. doi: 10.3390/ijms20236066.


The PPARs (peroxisome proliferator-activated receptors) play critical roles in the regulation of lipid and glucose metabolism. PPARδ, a member of the PPARs family, is associated with decreased susceptibility to ectopic lipid deposition and is implicated in the regulation of mitochondrial processes. The current study aimed to determine the role of PPARδ in fatty acid β-oxidation and its influence on PEPCK for the lipogenic/lipolytic balance during in vitro bovine oocyte maturation and embryo development. Activation of PPARδ by GW501516, but not 2-BP, was indicated by intact embryonic PEPCK (cytosolic) and CPT1 expression and the balance between free fatty acids and mitochondrial β-oxidation that reduced ROS and inhibited p-NF-κB nuclear localization. Genes involved in lipolysis, fatty acid oxidation, and apoptosis showed significant differences after the GW501516 treatment relative to the control- and 2-BP-treated embryos. GSK3787 reversed the PPARδ-induced effects by reducing PEPCK and CPT1 expression and the mitochondrial membrane potential, revealing the importance of PPARδ/PEPCK and PPARδ/CPT1 for controlling lipolysis during embryo development. In conclusion, GW501516-activated PPARδ maintained the correlation between lipolysis and lipogenesis by enhancing PEPCK and CPT1 to improve bovine embryo quality.

Keywords: 2-BP; CPT1; GSK3787; PEPCK; PPARδ; bovine blastocysts.

MeSH terms

  • Animals
  • Apoptosis
  • Carnitine O-Palmitoyltransferase / genetics*
  • Cattle
  • Embryonic Development / genetics*
  • Fatty Acids, Nonesterified / metabolism
  • Lipid Metabolism / genetics
  • Lipogenesis / drug effects
  • Lipolysis / drug effects
  • Mitochondria / drug effects
  • Mitochondria / genetics
  • Muscle, Skeletal / growth & development
  • Muscle, Skeletal / metabolism
  • Oxidation-Reduction
  • PPAR delta / genetics*
  • Phosphoenolpyruvate Carboxylase / genetics*
  • Thiazoles / pharmacology


  • Fatty Acids, Nonesterified
  • GW 501516
  • PPAR delta
  • Thiazoles
  • Carnitine O-Palmitoyltransferase
  • Phosphoenolpyruvate Carboxylase