PMID- 38020065
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231201
IS  - 1687-4757 (Print)
IS  - 1687-4765 (Electronic)
VI  - 2023
DP  - 2023
TI  - Peroxisome Proliferator-Activated Receptor gamma Regulates Lipid Metabolism in Sheep 
      Trophoblast Cells through mTOR Pathway-Mediated Autophagy.
PG  - 6422804
LID - 10.1155/2023/6422804 [doi]
LID - 6422804
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a key nuclear 
      receptor transcription factor that is highly expressed in trophoblastic cells 
      during embryonic attachment and is accompanied by rapid cell proliferation and 
      increased lipid accumulation. We previously showed that the autophagy pathway is 
      activated in cells after activation of PPARgamma, accompanied by increased lipid 
      accumulation. In this study, we used PPARgamma agonist rosiglitazone and inhibitor 
      GW9662, as well as autophagy activator rapamycin and inhibitor 3-methyladenine, 
      to unravel the probable mechanism of PPARgamma engaged in lipid metabolism in sheep 
      trophoblast cells (STCs). After 12 h, 24 h, and 48 h of drug treatment, the 
      levels of autophagy-related proteins were detected by Western blot, the 
      triglyceride content and MDA level of cells were detected by colorimetry, and the 
      lipid droplets and lysosomes were localized by immunofluorescence. We found that 
      PPARgamma inhibited the activity of mammalian target of rapamycin (mTOR) pathway in 
      STCs for a certain period of time, promoted the increase of autophagy and 
      lysosome formation, and enhanced the accumulation of lipid droplets and 
      triglycerides. Compared with cells whose PPARgamma function is activated, blocking 
      autophagy before activating PPARgamma will hinder lipid accumulation in STCs. 
      Pretreatment of cells with rapamycin promoted autophagy with results similar to 
      rosiglitazone treatment, while inhibition of autophagy with 3-methyladenine 
      reduced lysosome and lipid accumulation. Based on these observations, we conclude 
      that PPARgamma can induce autophagy by blocking the mTOR pathway, thereby promoting 
      the accumulation of lipid droplets and lysosomal degradation, providing an energy 
      basis for the rapid proliferation of trophoblast cells during embryo 
      implantation. In brief, this study partially revealed the molecular regulatory 
      mechanism of PPARgamma, mTOR pathway, and autophagy on trophoblast cell lipid 
      metabolism, which provides a theoretical basis for further exploring the 
      functional regulatory network of trophoblast cells during the attachment of sheep 
      embryos.
CI  - Copyright (c) 2023 Kexing Hao et al.
FAU - Hao, Kexing
AU  - Hao K
AD  - State Key Laboratory of Sheep Genetic Improvement and Healthy 
      Production/Institute of Animal Husbandry and Veterinary, Xinjiang Academy of 
      Agricultural and Reclamation Sciences, Shihezi, China.
AD  - College of Animal Science and Technology, Shihezi University, Shihezi 832000, 
      China.
FAU - Wang, Jing
AU  - Wang J
AD  - State Key Laboratory of Sheep Genetic Improvement and Healthy 
      Production/Institute of Animal Husbandry and Veterinary, Xinjiang Academy of 
      Agricultural and Reclamation Sciences, Shihezi, China.
AD  - College of Animal Science and Technology, Shihezi University, Shihezi 832000, 
      China.
FAU - Yu, Hengbin
AU  - Yu H
AD  - College of Animal Science and Technology, Shihezi University, Shihezi 832000, 
      China.
FAU - Chen, Lei
AU  - Chen L
AD  - College of Animal Science and Technology, Shihezi University, Shihezi 832000, 
      China.
FAU - Zeng, Weibin
AU  - Zeng W
AD  - College of Animal Science and Technology, Shihezi University, Shihezi 832000, 
      China.
FAU - Wang, Zhengrong
AU  - Wang Z
AUID- ORCID: 0000-0001-7169-2567
AD  - State Key Laboratory of Sheep Genetic Improvement and Healthy 
      Production/Institute of Animal Husbandry and Veterinary, Xinjiang Academy of 
      Agricultural and Reclamation Sciences, Shihezi, China.
FAU - Hu, Guangdong
AU  - Hu G
AUID- ORCID: 0000-0002-9710-6500
AD  - College of Animal Science and Technology, Shihezi University, Shihezi 832000, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20231108
PL  - United States
TA  - PPAR Res
JT  - PPAR research
JID - 101269101
PMC - PMC10651342
COIS- The authors have no conflicts of interest to declare.
EDAT- 2023/11/29 18:42
MHDA- 2023/11/29 18:43
PMCR- 2023/11/08
CRDT- 2023/11/29 14:38
PHST- 2023/08/04 00:00 [received]
PHST- 2023/10/03 00:00 [revised]
PHST- 2023/10/14 00:00 [accepted]
PHST- 2023/11/29 18:43 [medline]
PHST- 2023/11/29 18:42 [pubmed]
PHST- 2023/11/29 14:38 [entrez]
PHST- 2023/11/08 00:00 [pmc-release]
AID - 10.1155/2023/6422804 [doi]
PST - epublish
SO  - PPAR Res. 2023 Nov 8;2023:6422804. doi: 10.1155/2023/6422804. eCollection 2023.