Postprandial changes in gene expression of cholesterol influx and efflux mediators after intake of SFA compared with n -6 PUFA in subjects with and without familial hypercholesterolaemia: secondary outcomes of a randomised controlled trial.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 31448116 · doi:10.1017/jns.2019.25
What was done
Thirteen subjects with familial hypercholesterolaemia (FH; lipid-lowering treatment discontinued ≥4 weeks prior) and 14 normolipidaemic controls completed a randomised controlled double-blind crossover study. Participants consumed two single meals on separate test days, each containing 60 g of fat (~40% energy) enriched predominantly in either saturated fatty acids (SFA) or n-6 polyunsaturated fatty acids (PUFA). Peripheral blood mononuclear cells (PBMC) were isolated at fasting, 4 hours, and 6 hours postprandially. Expression of 33 lipid-related genes was measured using RT-qPCR and evaluated via linear mixed models.
What was found
A significant meal-by-group interaction occurred for MSR1 (P = 0.03), where SFA compared with n-6 PUFA caused a greater reduction in gene expression in controls only (P = 0.01). Across both groups (with no group interaction, P = 0.01 for all): SFA induced larger reductions in LDLR and FADS1/2 expression, smaller increases in INSIG1 and FASN expression, and larger increases in ABCA1 and ABCG1 expression compared with n-6 PUFA. Exact fold-change effect sizes and confidence intervals were not reported in the abstract.
Why it matters
The findings offer an acute postprandial molecular rationale for the known cholesterol-modulating effects of dietary fats, showing that SFA downregulates LDL clearance receptor gene expression and upregulates cholesterol efflux transporters relative to n-6 PUFA.
Limits
The total sample size was small (n = 27), and this was a secondary outcome analysis of an acute single-meal intervention. Gene expression was assessed in PBMCs rather than hepatic tissue, and the abstract omitted quantitative effect sizes and variance estimates beyond p-values.
Cited by
- supports Excess saturated fat intake inhibits sterol regulatory element-binding proteins in the liver, leading to fewer LDL receptors being produced.