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

Muhammad Idrees,Tabinda Sidrat,Myeong-Don Joo,Marwa El Sheikh,Lianguang Xu,Kyeong-Lim Lee,Seok-Hwan Song,Il-Keun Kong

doi:10.3390/ijms20236066

Muhammad Idrees, Tabinda Sidrat + Show 6 more

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https://doi.org/10.3390/ijms20236066

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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.

Highlights

Lipids are a potent source of energy, so considerable attention has been paid to their metabolism during in vitro oocyte maturation and early embryonic development [1]
PPARδ and PEPCK were expressed in cumulus cells as well as in GV oocytes, but at the MII stage, the expression of both the proteins were reduced
Management of energy stores is critical during oocyte maturation and early embryo development, and PPARs function as critical regulators of lipid and fatty acid homeostasis [1,10]

Summary

Introduction

Lipids are a potent source of energy, so considerable attention has been paid to their metabolism during in vitro oocyte maturation and early embryonic development [1]. Lipid contents and lipid-derived free fatty acid regulation have proven to be of great importance to oocyte developmental competence and early embryo physiology [2]. PPARδ, a ubiquitously expressed member of the PPARs family, plays a vital role in the transcription of many proteins related to lipid homeostasis [10]. PEPCK is highly associated with energy production and plays an important role in the homeostasis of lipids by re-esterification of free fatty acids to generate triglycerides [15,16,17]. Regulation/termination of PPARs in vivo or in vitro indicated that each receptor has physiological roles in gamete maturation and embryo development [22]

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Discussion

Conclusion