Apolipoprotein E (epsilon) genotype has a greater impact on apoB-48 than apoB-100 responses to dietary fat manipulation-insights from the SATgenε study.

SCOPE: To determine the contribution of intestinally and liver-derived lipoproteins to the postprandial plasma triacylglycerol (TAG) response in APOE3/E3 and E3/E4 individuals following chronic dietary fat manipulation.

METHODS AND RESULTS: In sequential order, participants (n = 12 E3/E3, n = 11 E3/E4) followed low fat; high-fat, high-saturated fat (HSF); and HSF with 3.45 g/day docosahexaenoic acid (HSF-DHA) diets, each for 8 weeks. After each dietary period, an acute test meal with a macronutrient profile representative of the dietary intervention was consumed. Apolipoprotein (apo)B isoforms were determined in isolated TAG-rich lipoprotein fractions (Svedberg flotation rate (Sf ) > 400, Sf 60-400, and Sf 20-60) by specific ELISA. A genotype × meal/diet interaction for the Sf > 400 fraction apoB-48 response (p < 0.05) was observed, with higher concentrations reached after the low fat than HSF-DHA meal in E4 carriers. This finding was associated with a lower TAG content of the Sf > 400 particles. Fasting Sf 60-400 and 20-60 apoB-48 concentrations were also significantly higher in E4 carriers. No impact of genotype on the apoB-100 responses was evident.

CONCLUSION: Our study revealed marked effects of dietary fat composition on the Sf > 400 apoB-48 response and particle TAG content in E4 carriers relative to the "wild-type" E3/E3 genotype, which suggest APOE genotype is a potential modulator of chylomicron particle synthesis.