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One plus one is … three? Evidence for a compounding effect of long-chain fatty acids on peroxisome proliferator-activated receptor activity.

S. Busato

Abstract:

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One plus one is … three? Evidence for a compounding effect of long-chain fatty acids on peroxisome proliferator-activated receptor activity.
S. Busato*, M. Bionaz. Oregon State University Corvallis, OR.

Peroxisome proliferator-activated receptors (PPAR) are transcription factors with known nutrigenomic response to fatty acids. In ruminants, PPAR control the expression of genes involved in lipid and glucose metabolism, anti-inflammatory response, and milk fat synthesis. While information on the in vitro potency to activate PPAR of some individual fatty acids exists, we were interested in exploring the activation of PPAR by a wider range of fatty acids and their combination. We hypothesized that the activation of PPAR with the combination of fatty acids is larger than the sum of the effect of individual fatty acids. We assessed in BFH-12 cells (immortalized bovine hepatocytes) the dose-response of 10 fatty acids common in bovine nutrition. PPAR activation was assessed by a gene reporter containing luciferase (3xPPAR response element) and normalized by renilla. Doses from 0 to 500 �M were applied using a HP D300e digital dispenser. Results were analyzed using GLM of SAS with dose as main effect and replicates (n = 4) as random. Response to each fatty acid was variable both in extent and in dose at maximum activation, with palmitic, stearic and dodecanoic acid showing the greatest impact on PPAR activation (3.5-fold, 3.7-fold and 4.3-fold vs. untreated control, respectively). Conversely, octanoic, myristic and linoleic acid displayed little to no effect. Cells were then treated with 2 fatty acids in combination, using only the 6 with the highest impact on PPAR activation, at the dose that maximizes PPAR activation. As hypothesized, the impact of 2 fatty acids in combination was greater than the sum of the activation of each individual fatty acid. The combinations of 3 fatty acids, each at a dose equal to one third of the optimal individual dose, resulted in a similar magnitude of effect on PPAR activation as compared with the combination of 2 fatty acids, while minimizing the total amount of fatty acids present in the medium. Our data indicates a greater nutrigenomic effect via PPAR of a mixture vs. single fatty acids, paving the way for the effective activation of PPAR isotypes in dairy cows through dietary means.

Keywords: long-chain fatty acids, peroxisome proliferator-activated receptors (PPAR), nutrigenomics.

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 nutrients with known or potential nutrigenomic effects in dairy cows, and their role in regulating gene expression. His work on PPAR has furthered the understanding of the role of fatty acids, both endogenous and exogenous, in the transition between pregnancy and parturition.