title: Fine 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.
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.
authors: Mammalian NutriPhysioGenomics, Division of Nutritional Sciences, 498 Animal Sciences Laboratory, Department of Animal Sciences, University of Illinois, Urbana, IL 61801, USA.
authors: Massimo
authors: M
authors: Bionaz
authors: Betsy J
authors: BJ
authors: Thering
authors: Juan J
authors: JJ
authors: Loor
mesh_terms: D000818:Animals; D002417:Cattle; D002460:Cell Line; D004041:Dietary Fats / Q000378:metabolism; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D020869:Gene Expression Profiling / Q000662:veterinary; D005786:Gene Expression Regulation / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008958:Models, Molecular; D054647:Nutrigenomics / Q000379:methods*; D047493:PPAR alpha / Q000819:agonists / Q000737:chemistry / Q000378:metabolism*; D020025:Peroxisome Proliferators / Q000494:pharmacology; D011487:Protein Conformation; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020218:Response Elements; D015398:Signal Transduction / Q000187:drug effects; D044242:Trans Fatty Acids / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D018836:Inflammation Mediators; D047493:PPAR alpha; D020025:Peroxisome Proliferators; D011743:Pyrimidines; D012333:RNA, Messenger; D044242:Trans Fatty Acids; C006253:pirinixic acid