Intestinally produced triglyceride-rich lipoproteins (TRL) play an important role in the progression of atherosclerosis. In this study, we investigated the relevance of monounsaturated fatty acid (MUFA) and saturated fatty acid (SFA) in postprandial TRL in affecting the transcriptional activity of the apolipoprotein-B48 receptor (ApoB48R) and its functionality in human monocyte/macrophage cells. Healthy male volunteers were administered four standardized high-fat meals containing butter, high-palmitic sunflower oil, olive oil (ROO) or a mixture of vegetable and fish oils (50 g/m(2) body surface area) to obtain a panel of postprandial TRL with gradual MUFA oleic acid-to-SFA palmitic acid ratios. The increase in this ratio was linearly associated with a decrease of ApoB48R up-regulation and lipid accumulation in THP-1 and primary monocytes. ApoB48R mRNA levels and intracellular triglycerides were also lower in the monocytes from volunteers after the ingestion of the ROO meal when compared to the ingestion of the butter meal. In THP-1 macrophages, the increase in the MUFA oleic acid-to-SFA palmitic acid ratio in the postprandial TRL was linearly correlated with an increase in ApoB48R down-regulation and a decrease in lipid accumulation. We also revealed that the nuclear receptor transcription factors PPARα, PPARβ/δ, and PPARγ and the PPAR-RXR transcriptional complex were involved in sensing the proportion of MUFA oleic acid and SFA palmitic acid, and these were also involved in adjusting the transcriptional activity of ApoB48R. The results of this study support the notion that MUFA-rich dietary fats may prevent excessive lipid accumulation in monocyte/macrophage cells by targeting the postprandial TRL/ApoB48R axis.
Keywords: 9-cis-retinoic acid; 9cRA; ABCA1; ACAT; ATP-binding cassette transporter A1; ApoB48R; Apolipoprotein-B48 receptor; C-terminal helix; H; HPRT; HPSO; LBD; LBP; MUFA; MUFA oleic acid; Macrophages; Monocytes; PMA; PPAR; PPRE; Postprandial triglyceride-rich lipoproteins; ROO; RPLP0; RXR; SFA; SFA palmitic acid; TRL; VEFO; acyl-CoA:cholesterol acyltransferase; apolipoprotein-B48 receptor; high-palmitic sunflower oil; hypoxanthine phosphoribosyltransferase; ligand binding domain; ligand binding pocket; mixture of vegetable and fish oils; monounsaturated fatty acids; olive oil; peroxisome proliferated activated receptor; peroxisome proliferator responsive elements; phorbol 12-myristate-13-acetate; qRT-PCR; quantitative reverse transcription polymerase chain reaction; retinoid X receptor; ribosomal protein large P0; saturated fatty acids; siRNA; small interfering RNA; triglyceride-rich lipoproteins.
© 2013.