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A hybrid hepatic tissue model to highlight changes in peroxisome-proliferator activated receptor activity through the peripartum period.

S. Busato




A hybrid hepatic tissue model to highlight changes in peroxisome-proliferator activated receptor activity through the peripartum period.
S. Busato*1, A. M. Abdelatty2,1, M. Bionaz1. 1Oregon State University Corvallis, OR, 2Cairo University Cairo, Egypt.

The transition from pregnancy to lactation imposes a large degree of metabolic stress on dairy cows, when the overall negative energy balance causes lipolysis and release of fat in the form of nonesterified fatty acids (NEFA). In prior studies, we proved that circulating NEFA activate the peroxisome-proliferator activated receptors (PPAR) in a hybrid in vitro-in vivo model, where immortalized cells were treated with serum at different NEFA concentrations. PPAR are involved in the metabolism of fatty acids and triglycerides (TAG), as well as in the regulation of insulin sensitivity, all crucial processes in the peripartum. Our objective was to assess the role of PPAR activation in the transition period through an ex vivo bovine liver model. Our hypothesis was that activation of PPAR, measurable through changes in gene expression, would be modulated by serum NEFA through the peripartum. Four primiparous Jersey cows received trocar biopsies at −10 and + 10 DIM, and the tissue was sectioned using a Krumdieck Tissue Slicer to obtain thin slices (PCLS) suitable for culture. Two PCLS were then incubated with each treatment: NEFA isolated from serum, as well as whole serum, and isotype-specific synthetic agonists and antagonists of PPAR, applied individually. Transcription of PPAR target genes was measured via RTqPCR, and analyzed through PROC MIXED of SAS 9.4, comparing treatment and DIM effect, and their interaction. Despite large variation between animals, expression of PPARA, PPARG and FABP1 decreased while transcription of PDK4 increased from −10 to +10 DIM. Treatment with a PPARγ agonist increased expression of ACADVL and LIPC at +10 DIM. NEFA and a PPARδ antagonist decreased PDK4 expression, and C 16:0 upregulated transcription of FABP1. Whole-transcriptome sequencing revealed that treatment of PCLS with PPAR agonists in the postpartum modulates the expression of genes involved in lipid metabolism, as well as amino and nucleic acid metabolism. Despite the changes in gene expression, no change was observed in the TAG concentration in response to PPAR activation. Our findings suggest that our PCLS model is informative at a molecular level.

Keywords: nutrigenomics, peripartum, peroxisome-proliferator activated receptors (PPAR).

Biography: Sebastiano Busato is a doctoral student at Oregon State University. Under the guidance of Dr. Massimo Bionaz, his research focuses on the study of bioactive compounds with known or potential nutrigenomic effects in dairy cows, and their role in regulating gene expression.