Abstract P420: Dietary Fat on Whole Blood Gene Expression and Plasma Lipids in the Framingham Heart Study

Objective: To describe the influence of type of dietary fat on the activity of metabolic pathways, as measured by gene expression profiles, and the relation to plasma lipids. Background: Metabolic studies have demonstrated strong associations of dietary fatty acid composition with plasma lipids. Relatively little is known about the pathways and gene expression changes that mediate these relationships in the general population. Methods: We analyzed self-reported dietary intake of fatty acids, plasma lipid levels, and genome-wide gene expression data from Framingham Heart Study Offspring and Third Generation cohort participants. We excluded participants on lipid therapy. Multivariable linear regression models were conducted with plasma lipids as separate outcomes, energy-adjusted residuals of dietary fats as predictors, and adjustment for clinical and dietary covariates. Normalized gene expression from whole blood derived RNA was similarly modeled with additional adjustment for cell count and batch effects. Results: Among 3681 participants, higher polyunsaturated fatty acid (PUFA) intake is associated with lower LDL-C (estimated β [regression coefficient] = -0.5, p=0.002), higher HDL-C (β= 0.4, p<0.0001), and lower triglyceride (β= -0.009, p=0.0003) concentrations after adjustment for age, sex, carbohydrate, protein, and alcohol intake. Higher PUFA intake was associated with differential gene expression of cholesterol efflux transporters (ABCA1/ABCG1), LDL receptor degrader (IDOL), and non-lipoprotein metabolism related transcripts (FDR < 0.05). In contrast, higher saturated fat intake (SFA) showed inverse associations with ABCA1 expression levels and HDL cholesterol ( Figure 1 ). Conclusions: Higher PUFA intake is associated with a less atherogenic lipid profile and higher ABCA1 expression with inverse associations for higher SFA intake. Gene expression analysis reveals important links between dietary fat type, specific cholesterol metabolism pathways, and lipids in a community cohort.