Raised levels of intestinally derived lipoproteins before and after a fat containing meal have been associated with an increased cardiovascular disease risk( 1 ). Given the pivotal role that apolipoprotein (apo)E plays in the clearance of triacylglycerol (TAG)-rich lipoproteins, the APOE genotype is now considered to be an important genetic determinant of the responsiveness of plasma lipids to dietary fat manipulation. Although both meal fat quantity and quality influence the postprandial Sf>400 (chylomicron) apoB-48 response, little is known about the interactions of these dietary variables with APOE genotype.
Male participants (mean age 53 (sd 9) y and BMI 25.8 (sd 2.6) kg/m2) prospectively recruited according to APOE genotype (n=12 E3/E3, n=11 E3/E4), were assigned to a low-fat diet (LF), high-fat, high saturated fat diet (HSF), and HSF diet with 3.45 g/d docosahexaenoic acid (HSF-DHA), each for an 8 week period in the same order. At the end of each dietary period, a test meal with a macronutrient profile representative of the dietary intervention was consumed and blood samples collected at regular intervals for the isolation of the Sf>400 fraction. TAG was analysed using an automated assay and apoB-48 by specific ELISA( 2 ).
A significant interaction between genotype and diet/test meal composition was found for the Sf>400 apoB-48 response (Figure), with a 45% lower area under the curve after the HSF-DHA than LF diet/test meal in the APOE4 carriers (P=0.008). We have previously reported a similar relationship for the Sf>400 cholesterol response( 3 ). There was no significant impact of APOE genotype or diet/test meal composition on the Sf>400 TAG response.
Mean ± sem for the Sf>400 apoB-48 response over 480 min after consumption of test meals representative of the LF diet (□), HSF diet (•) and HSF-DHA diet (○) in A) the APOE3/E3 group (n=12) and B) the APOE3/E4 group (n=11). There was a significant diet/test meal*genotype interaction (P=0.030).
In conclusion, our study has revealed APOE genotype to influence the metabolism of large TAG-rich dietary derived lipoproteins to diets/meals of varying fat quantity and quality, with the greater apoB-48 (and cholesterol) response to the LF test meal in APOE4 carriers worthy of further investigation.
This work was funded by the Wellcome Trust (WT085045MA).