PMID- 35903133
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220731
IS  - 2297-1769 (Print)
IS  - 2297-1769 (Electronic)
IS  - 2297-1769 (Linking)
VI  - 9
DP  - 2022
TI  - Peroxisome Proliferator-Activated Receptor Activation in Precision-Cut Bovine 
      Liver Slices Reveals Novel Putative PPAR Targets in Periparturient Dairy Cows.
PG  - 931264
LID - 10.3389/fvets.2022.931264 [doi]
LID - 931264
AB  - Metabolic challenges experienced by dairy cows during the transition between 
      pregnancy and lactation (also known as peripartum), are of considerable interest 
      from a nutrigenomic perspective. The mobilization of large amounts of 
      non-esterified fatty acids (NEFA) leads to an increase in NEFA uptake in the 
      liver, the excess of which can cause hepatic accumulation of lipids and 
      ultimately fatty liver. Interestingly, peripartum NEFA activate the Peroxisome 
      Proliferator-activated Receptor (PPAR), a transcriptional regulator with known 
      nutrigenomic properties. The study of PPAR activation in the liver of 
      periparturient dairy cows is thus crucial; however, current in vitro models of 
      the bovine liver are inadequate, and the isolation of primary hepatocytes is time 
      consuming, resource intensive, and prone to errors, with the resulting cells 
      losing characteristic phenotypical traits within hours. The objective of the 
      current study was to evaluate the use of precision-cut liver slices (PCLS) from 
      liver biopsies as a model for PPAR activation in periparturient dairy cows. Three 
      primiparous Jersey cows were enrolled in the experiment, and PCLS from each were 
      prepared prepartum (-8.0 +/- 3.6 DIM) and postpartum (+7.7+/- 1.2 DIM) and treated 
      independently with a variety of PPAR agonists and antagonists: the PPARalpha agonist 
      WY-14643 and antagonist GW-6471; the PPARdelta agonist GW-50156 and antagonist 
      GSK-3787; and the PPARgamma agonist rosiglitazone and antagonist GW-9662. Gene 
      expression was assayed through RT-qPCR and RNAseq, and intracellular 
      triacylglycerol (TAG) concentration was measured. PCLS obtained from postpartum 
      cows and treated with a PPARgamma agonist displayed upregulation of ACADVL and LIPC 
      while those treated with PPARdelta agonist had increased expression of LIPC, PPARD, 
      and PDK4. In PCLS from prepartum cows, transcription of LIPC was increased by all 
      PPAR agonists and NEFA. TAG concentration tended to be larger in tissue slices 
      treated with PPARdelta agonist compared to CTR. Use of PPAR isotype-specific 
      antagonists in PCLS cultivated in autologous blood serum failed to decrease 
      expression of PPAR targets, except for PDK4, which was confirmed to be a PPARdelta 
      target. Transcriptome sequencing revealed considerable differences in response to 
      PPAR agonists at a false discovery rate-adjusted p-value of 0.2, with the most 
      notable effects exerted by the PPARdelta and PPARgamma agonists. Differentially expressed 
      genes were mainly related to pathways involved with lipid metabolism and the 
      immune response. Among differentially expressed genes, a subset of 91 genes were 
      identified as novel putative PPAR targets in the bovine liver, by 
      cross-referencing our results with a publicly available dataset of predicted PPAR 
      target genes, and supplementing our findings with prior literature. Our results 
      provide important insights on the use of PCLS as a model for assaying PPAR 
      activation in the periparturient dairy cow.
CI  - Copyright (c) 2022 Busato, Ford, Abdelatty, Estill and Bionaz.
FAU - Busato, Sebastiano
AU  - Busato S
AD  - Department of Animal and Rangeland Sciences, Oregon State University, Corvallis, 
      OR, United States.
FAU - Ford, Hunter R
AU  - Ford HR
AD  - Department of Animal and Rangeland Sciences, Oregon State University, Corvallis, 
      OR, United States.
FAU - Abdelatty, Alzahraa M
AU  - Abdelatty AM
AD  - Department of Nutrition and Clinical Nutrition, Faculty of Veterinary Medicine, 
      Cairo University, Giza, Egypt.
FAU - Estill, Charles T
AU  - Estill CT
AD  - Department of Animal and Rangeland Sciences, Oregon State University, Corvallis, 
      OR, United States.
AD  - College of Veterinary Medicine, Oregon State University, Corvallis, OR, United 
      States.
FAU - Bionaz, Massimo
AU  - Bionaz M
AD  - Department of Animal and Rangeland Sciences, Oregon State University, Corvallis, 
      OR, United States.
LA  - eng
PT  - Journal Article
DEP - 20220712
PL  - Switzerland
TA  - Front Vet Sci
JT  - Frontiers in veterinary science
JID - 101666658
PMC - PMC9315222
OTO - NOTNLM
OT  - PCLS
OT  - PPAR
OT  - dairy cows
OT  - liver
OT  - nutrigenomics
OT  - peripartum
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/07/30 06:00
MHDA- 2022/07/30 06:01
PMCR- 2022/01/01
CRDT- 2022/07/29 01:54
PHST- 2022/04/28 00:00 [received]
PHST- 2022/06/06 00:00 [accepted]
PHST- 2022/07/29 01:54 [entrez]
PHST- 2022/07/30 06:00 [pubmed]
PHST- 2022/07/30 06:01 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fvets.2022.931264 [doi]
PST - epublish
SO  - Front Vet Sci. 2022 Jul 12;9:931264. doi: 10.3389/fvets.2022.931264. eCollection 
      2022.