Postprandial changes in gene expression of cholesterol influx and effluxmediators after intake of SFA compared withn-6 PUFA in subjects with andwithout familial hypercholesterolaemia: secondary outcomes of arandomised controlled trial

Abstract

The long-term cholesterol-lowering effect of replacing intake of SFA with PUFA is well established, but has not been 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 hypercholesterolaemia (FH). Thirteen subjects with FH (who had discontinued lipid-lowering treatment≥4 weeksprior to both test days) and fourteen normolipidaemic controls were included in a randomised controlled double-blind crossover study with twomeals, each with 60 g of fat either mainly SFA (about 40% energy) orn-6 PUFA (about 40% energy). PBMC were isolated in fasting, and 4 and 6 h post-prandial blood samples. Expression of thirty-three lipid genes was analysed by reverse transcription quantitative PCR. A linear mixed model was usedtoassess postprandial effects between meals and groups. There was a significant interaction between meal and group forMSR1(P=0·03), where intake ofSFA compared withn-6 PUFA induced a larger reduction in gene expression in controls only (P=0·01). Intake of SFA compared withn-6 PUFA inducedlarger reductions in gene expression levels ofLDLRandFADS1/2, smaller increases ofINSIG1andFASN, and larger increases ofABCA1andABCG1(P=0·01 for all, no group interaction). Intake of SFA compared withn-6 PUFA induced changes in gene expression of cholesterol influx and efflux med-iators in PBMC including lowerLDLRand higherABCA1/G1, potentially explaining the long-term cholesterol-raising effect of a high SFA intake.