When Two plus Two Is More than Four: Evidence for a Synergistic Effect of Fatty Acids on Peroxisome Proliferator-Activated Receptor Activity in a Bovine Hepatic Model.

ABSTRACT

The inclusion of fat in livestock diets represents a valuable and cost-effective way to increase the animal's caloric intake. Beyond their caloric value, fatty acids can be understood in terms of their bioactivity, via the modulation of the ligand-dependent nuclear peroxisome proliferator-activated receptors (PPAR). Isotypes of PPAR regulate important metabolic processes in both monogastric and ruminant animals, including the metabolism of fatty acids (FA), the production of milk fat, and the immune response; however, information on the modulation of bovine PPAR by fatty acids is limited. The objective of this study was to expand our understanding on modulation of bovine PPAR by FA, both when used individually and in combination, in an immortalized cell culture model of bovine liver. Of the 10 FA included in the study, the greatest activation of the PPAR reporter was detected with saturated FA C120, C160, and C180, as well as phytanic acid, and the unsaturated FA C161 and C181. When supplemented in mixtures of 2 FA, the most effective combination was C120 + C160, while in mixtures of 3 FA, the greatest activation was caused by combinations of C120 with C160 and either C180, C161, or C181. Some mixtures display a synergistic effect that leads to PPAR activation greater than the sum of their parts, which may be explained by structural dynamics within the PPAR ligand-binding pocket. Our results provide fundamental information for the development of tailored dietary plans that focus on the use of FA mixtures for nutrigenomic purposes.