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

Abstract

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.

Advances in fatty acids nutrition in dairy cows: from gut to cells and effects on performance

“…In monogastrics this PPAR isotype is a pivotal player in adipogenesis and insulin sensitivity, but in dairy cows it has been specifically studied for its role in modulating milk fat synthesis [248][249][250], its involvement in the mTOR pathway, particularly mTORC2 [251], and its anti-inflammatory role [4,5]. All PPAR isotypes play a role in improving reproductive parameters of dairy cows, such as the mitigation of endometritis [252], contribution to folliculogenesis [253], reproductive hormone synthesis [253], and the development of embryos [254]. All PPAR isotypes were found to be upregulated in response to naturally occurring prostaglandins in bovine uterine cells [255].…”

Dexmedetomidine protects cardiac microvascular endothelial cells from the damage of ogd/r through regulation of the pparδ‐mediated autophagy

“…To analyze the effects of Dex on OGD/R‐induced injury, cells were divided into four groups: control group, OGD/R group, OGD/R+Dex (0.1 nM) group, and OGD/R+Dex (1 nM) group. To investigate the underlying mechanism, cells were pretreated with 8 mM 3‐methyladenine 13 (3MA, an autophagy inhibitor, Sigma), 10 μM GSK3787 14 (PPARδ antagonist, MCE, shanghai, China), or 10 μM GW 501516 15 (PPARδ agonist, MCE, Shanghai, China) for 24 h before OGD/R and Dex treatment.…”

Constitutive Expression of TERT Enhances β-Klotho Expression and Improves Age-Related Deterioration in Early Bovine Embryos

“…Mitochondrial ∆Ψ m in blastocysts was analyzed via staining with JC-1 (Molecular Probes, Invitrogen, Carlsbad, CA, USA) [ 39 ]. Briefly, day-8 blastocysts were collected and fixed in 4% paraformaldehyde, washed, and incubated with 10 mg/mL JC-1 dye prepared in PBS/PVP solution at 37 °C for 1 h under dark conditions.…”