Graduate Thesis Or Dissertation
 

Molecular Nutrition in Dairy Cows: Modulation of Peroxisome Proliferator-Activated Receptors through Nutrigenomic Approaches

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https://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/kh04dx519

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  • Nutrigenomics is a branch of nutrition that seeks to elucidate the relationship between dietary components and expression of genes. Certain bioactive compounds present in the diet have the potential to modulate transcription of genes through their interactions with ligand-dependent nuclear receptors, a series of transcriptional regulators capable of sensing intracellular concentrations of a specific compound and induce or repress downstream target genes affecting metabolic and signaling pathways. Among nuclear receptors with known nutrigenomic properties, the Peroxisome Proliferator-activated Receptors (PPAR), whose natural ligands are fatty acids, eicosanoids, and leukotrienes, are of particular interest. The three known isotypes of PPAR (PPARα, PPARβ/δ and PPARγ) are involved in the regulation of a variety of metabolic pathways such as fatty acid catabolism and lipogenesis, but they also control inflammation and the immune response. Crucially, the pathways modulated by PPAR are essential in ensuring adequate physiological fitness and performance of dairy cows, especially during metabolically challenging periods such as the transition between pregnancy and lactation. Dairy cows experience a variety of metabolic stressors during the peripartum (the period between 3 weeks before to 3 weeks after parturition), mainly as a result of the combination of a sudden increase in energy demands and a reduction in feed intake. During this period, the liver acquires a central role, as it is tasked with maintaining homeostasis through increased rates of gluconeogenesis, and with metabolizing increasing rates of non-esterified fatty acids (NEFA) released from the adipose tissue to cope with the caloric imbalances. In chapter 2, a hybrid in vivo-in vitro approach is presented, in which the natural cellular environment is mimicked by culturing immortalized bovine cells in blood serum from periparturient cows; within that experiment, it is demonstrated that high circulating NEFA activate PPAR (preferentially PPARβ/δ and PPARγ) in a dose-response fashion. Chapter 3 aims to provide a more representative model of the bovine liver, with the culture of precision-cut liver slices (PCLS) obtained from dairy cows at -10 and +10 day relative to parturition as a potential model for PPAR activation in the peripartum. The findings reveal a relatively modest response of PCLS to synthetic PPAR activators in terms of the transcriptional landscape. Results from the manuscripts presented in chapters 2 and 3 provide information on the consequences of PPAR activation within the peripartum. The implementation of nutrigenomics-based dietary plan for dairy cows must rely on the precise quantification of the effect of fatty acids on the metabolism and physiology of the animal. Though supplemental dietary lipids have well-understood effects in terms of productive parameters in dairy cows, their ability to modulate the transcriptome through PPAR activation is virtually unknown. In chapter 4, we set out to quantify the effect of individual fatty acids on PPAR activity using an immortalized cell model, and we design mixtures of fatty acids that synergistically maximize PPAR activation. In chapter 5, those results were confirmed and adjusted for mid-lactation dairy cows; the resulting mixtures were formulated and supplemented to the diets of mid-lactation dairy cows and resulting effects on the transcriptome were quantified. The impacts, though modest in their magnitude, hint at the possibility of developing dietary plans to fine-tune the cow’s metabolism through PPAR activation, especially if reconfiguration of fatty acid profiles in the adipose tissue is considered.
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  • Pending Publication
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  • 2021-09-07 to 2024-01-11

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