Abstract/Summary

Reducing dietary saturated fat (SFA) intake via replacing it with unsaturated fatty acids (UFA) is a public healthy strategy for cardiovascular disease (CVD) prevention. However, with some studies reporting inter-individual variability in the low-density lipoprotein cholesterol (LDL-C) response to lowering dietary SFA, there is considerable interest in potential determinants underlying the responsiveness of LDL-C to fat intake. Human studies suggest that dietary fat composition affects body fat distribution with higher SFA intakes proposed to be associated with abdominal fat accumulation and greater CVD risk. However, it is not clear whether the variability in LDL-C response to dietary SFA intake is related to changes in body composition. The relationship between dietary SFA intake with CVD risk markers and body composition was investigated using a cross-sectional (BODYCON, Chapter 2) and an 8-week sequential dietary intervention (RISSCI, Chapter 3) study. BODYCON included 409 healthy adults aged 18-70y, with data collected for total body composition, dietary intake, physical activity levels and circulating CVD risk markers. Although dietary SFA and abdominal visceral adipose tissue explained 9% of the variability in LDL-C, there was a lack of a dose-dependent relationship between increasing quartiles of dietary SFA%TE intake and these determinants, with total and LDL-C concentrations lower in Q2 (10.1-11.9%TE) than Q4 (14.9-38.7%TE) (p≤0.05). Of the anthropometric measures, only lean mass within the trunk (android) region was greater in Q3 (12.0-14.8%TE) compared to Q1 (1.9-10.0%TE) (p=0.02). Therefore, findings from the BODYCON study suggested that the effect of dietary SFA on LDL-C may be independent of body fat distribution. In the RISSCI study (n=41/109), significant reductions in fasting lipids (total, high density lipoprotein and LDL-C and triacylglycerol) (on average 10-15%, p<0.01) and percentage of android body fat were evident after replacing 8% dietary SFA with UFA. This suggested that, in the RISSCI study, the beneficial effects of replacing dietary SFA with UFA on lipid CVD risk markers was associated with a reduction in central obesity in healthy men. To provide insights into the mechanisms underlying the effects of dietary fat on LDL-C, the expression of genes involved in cholesterol metabolism were measured in a subset of the RISSCI participants (n=58/109). Compared with the high SFA diet, there was an upregulation of the LDL-receptor, ABCG1 and NR1H3 mRNA gene expression in peripheral blood mononuclear cells (PBMC) after the low SFA diet. To determine whether the variability in the LDL-C response to dietary SFA intake (-39% to +19%) was associated with changes in PBMC gene expression, the group was then stratified into responder (n=12) and non-responders (n=13) according to actual change in LDL-C in response to the change in dietary fat composition. Interestingly, prior to the start of the intervention, the fasting LDL-C concentration was 19% lower in non-responders compared to responders with a significant reduction in fasting lipids after replacing dietary SFA with UFA only evident in the responders group (p≤0.05). Although there was a non-significant tendency for the LDL-R mRNA expression to be increased in both responder and non-responders after replacing dietary SFA with UFA, it was only in non-responders that the ABCG1 and NR1H3 mRNA expressions were significantly upregulated after the low SFA diet (p≤0.01) (Chapter 4). Studies investigating the associations between APOLIPOPROTEIN (APO)E genotype with CVD risk markers have generated inconsistent results, with a small number of studies suggesting that BMI plays an important role in this relationship. Using data from BODYCON (n=360), fasting blood lipids were found to be lower in the APOE2/E3 than the APOE3/E3 group and APOE4 carriers in the normal BMI subgroup only (p≤0.04) (Chapter 5). Lower dietary fibre (g) and trans-fat (%TE) intake in the APOE2/E3 participants than APOE4 carriers, and a lower carbohydrate (%TE) intake relative to the APOE3/E3 group were also evident in the normal BMI subgroup. APOE x BMI interactions on body weight and android fat mass were observed (p≤0.01). While lean mass was higher in APOE4 carriers than APOE3/E3 in the normal BMI subgroup (p=0.02), the android:gynoid fat ratio was lower in APOE4 carriers than APOE3/E3 in the overweight/obese subgroup (p=0.04). Future studies should confirm the APOE-body composition association. In summary, by using a combination of cross-sectional and interventional study designs, this thesis has generated novel findings into the role of dietary SFA on CVD risk markers, body fat distribution and responsiveness of genes regulating cholesterol metabolism to dietary fat manipulation. More studies are needed to determine mechanisms underlying the inter-individual variability in LDL-C response to dietary fat manipulation and to confirm APOE body composition association to provide more effective personalised dietary advice.