TitleFine metabolic regulation in ruminants via nutrient-gene interactions: saturated long-chain fatty acids increase expression of genes involved in lipid metabolism and immune response partly through PPAR-α activation.
Publication TypeJournal Article
Year of Publication2012
AuthorsBionaz, M, Thering, BJ, Loor, JJ
JournalBr J Nutr
Volume107
Issue2
Pagination179-91
Date Published2012 Jan
ISSN1475-2662
KeywordsAnimals, Cattle, Cell Line, Dietary Fats, Fatty Acids, Fatty Acids, Unsaturated, Gene Expression Profiling, Gene Expression Regulation, Inflammation Mediators, Lipid Metabolism, Models, Molecular, Nutrigenomics, Peroxisome Proliferators, PPAR alpha, Protein Conformation, Pyrimidines, Response Elements, RNA, Messenger, Signal Transduction, Trans Fatty Acids
Abstract

Madin-Darby Bovine Kidney cells cultured with 150 μm of Wy-14 643 (WY, PPARα agonist) or twelve long-chain fatty acids (LCFA; 16 : 0, 18 : 0, cis-9-18 : 1, trans-10-18 : 1, trans-11-18 : 1, 18 : 2n-6, 18 : 3n-3, cis-9, trans-11-18 : 2, trans-10, cis-12-18 : 2, 20 : 0, 20 : 5n-3 and 22 : 6n-3) were used to uncover PPAR-α target genes and determine the effects of LCFA on expression of thirty genes with key functions in lipid metabolism and inflammation. Among fifteen known PPAR-α targets in non-ruminants, ten had greater expression with WY, suggesting that they are bovine PPAR-α targets. The expression of SPP1 and LPIN3 was increased by WY, with no evidence of a similar effect in the published literature, suggesting that both represent bovine-specific PPAR-α targets. We observed the strongest effect on the expression of PPAR-α targets with 16 : 0, 18 : 0 and 20 : 5n-3.When considering the overall effect on expression of the thirty selected genes 20 : 5n-3, 16 : 0 and 18 : 0 had the greatest effect followed by 20 : 0 and c9t11-18 : 2. Gene network analysis indicated an overall increase in lipid metabolism by WY and all LCFA with a central role of PPAR-α but also additional putative transcription factors. A greater increase in the expression of inflammatory genes was observed with 16 : 0 and 18 : 0. Among LCFA, 20 : 5n-3, 16 : 0 and 18 : 0 were the most potent PPAR-α agonists. They also affected the expression of non-PPAR-α targets, eliciting an overall increase in the expression of genes related to lipid metabolism, signalling and inflammatory response. Data appear to highlight a teleological evolutionary adaptation of PPAR in ruminants to cope with the greater availability of saturated rather than unsaturated LCFA.

DOI10.1017/S0007114511002777
Alternate JournalBr. J. Nutr.
PubMed ID21729373