Abstract
The long-term cholesterol lowering effect of replacing intake of saturated fatty acids (SFAs) with polyunsaturated fatty acids (PUFAs) is well established, however not fully explained mechanistically. We examined the postprandial response of meals with different fat quality on expression of lipid genes in peripheral blood mononuclear cells (PBMC) in subjects with and without familial hypercholesterolemia (FH). Thirteen subjects with FH (who had discontinued lipid-lowering treatment ≥4 weeks prior to both test days) and 14 normolipidemic controls were included in a randomized controlled double-blind crossover study with two meals, each with 60 grams of fat either mainly SFAs (~40 E%) or n-6 PUFAs (~40 E%). PBMCs were isolated in fasting, and 4 and 6 hours postprandial blood samples. Expression of 33 lipid genes was analysed by reverse transcription quantitative polymerase chain reaction. A linear mixed model was used to assess postprandial effects between meals and groups. There was a significant interaction between meal and group for MSR1 (p=0.03), where intake of SFAs compared to n-6 PUFAs induced a larger reduction in gene expression in controls only (p=0.01). Intake of SFAs compared to n-6 PUFAs induced larger reduction in gene expression levels of LDLR and FADS1/2, smaller increase of INSIG1 and FASN, and larger increase of ABCA1 and ABCG1 (p=0.01 for all, no group interaction). Intake of SFAs compared to n-6 PUFAs induced changes in gene expression of cholesterol influx and efflux mediators in PBMCs including lower LDLR and higher ABCA1/G1, potentially explaining the long-term cholesterol-raising effect of a high SFA intake.
Postprandial changes in gene expression of cholesterol influx and efflux mediators after intake of SFA compared to n-6 PUFA in subjects with and without familial hypercholesterolemia – secondary outcomes of a randomized controlled trial