Effect of Synthetic Ligands of PPAR α, β/δ, γ, RAR, RXR and LXR on the Fatty Acid Composition of Phospholipids in Mice

Abstract

Nuclear hormone receptors are transcription factors that can be activated by nutrition-derived ligands and alter the expression of various specific target genes. Stearoyl-Coenzyme A desaturase (SCD1) converts palmitic acid (16:0) to palmitoleic acid (16:1n-7) as well as stearic acid (18:0) to oleic acid (18:1n-9). At the same time, elongase 6 (ELOVL6) elongates 16:1n-7 and 18:1n-9 to vaccenic acid (18:1n-7) and eicosenoic acid (20:1n-9). We examined how synthetic selective ligands of nuclear hormone receptors alter the gene expression of hepatic enzymes in mice. In addition, we examined how the regulation of these two enzymes influences fatty acid composition of phospholipids in liver and plasma. Mice were gavaged daily for 1 week with synthetic ligands of peroxisome proliferator-activated receptor (PPAR) α, β/δ, γ, liver X receptor (LXR), retinoic acid receptor (RAR) and retinoid-X receptor (RXR) for 1 week. Phospholipids from liver and plasma were analysed using ESI-MS/MS and GC after saponification. Hepatic gene expression of SCD1 and ELOVL6 was measured using QRT-PCR. SCD1 and ELOVL6 expression increased after the gavage of LXR and RXR ligands. The analysis of fatty acid composition of total phospholipids in plasma and liver showed increased percentage contributions of the SCD1 and ELOVL6 products 18:1n-9, 18:1n-7 and 20:1n-9 after LXR and RXR ligand application. Analysis of total phospholipids from plasma and liver revealed a significant increase in monounsaturated fatty acids bound in phosphatidylcholine (PtdCho) and lysophosphatidylcholine (PtdEtn) after LXR and RXR ligand administration. Increased hepatic gene expression of SCD1 and ELOVL6 after gavage of selective RXR or LXR ligands to mice resulted in increased concentrations of their metabolic products in phospholipids of liver and plasma.