Abstract 14941: Substitution of Dietary Saturated Fatty Acids With Omega-6 Polyunsaturated Fatty Acids Decreases LDL ApoB-100 Production Rate in Men With Dyslipidemia Associated With Insulin-Resistance
Introduction: The consumption of omega (n)-6 polyunsaturated fatty acids (PUFA) in replacement of saturated fatty acids (SFA) is advocated to prevent cardiovascular disease (CVD) as it is recognized to reduce LDL-C concentrations. However, the impact of this substitution on lipoprotein metabolism in dyslipidemic and insulin-resistant (IR) subjects remains unclear, limiting our ability to elaborate optimal dietary guidelines for this population with high CVD risk.
Hypothesis: Substitution of SFA with n-6 PUFA reduces the production rate (PR), stimulates the fractional catabolic rate (FCR) of apolipoprotein (apo) B-containing lipoproteins, and regulates the intestinal expression of key genes involved in lipoprotein metabolism in IR subjects.
Methods: Thirty dyslipidemic and IR men (triglyceride levels: 2.25 ± 1.02 mmol/L; HOMA-IR: 4.46 ± 1.19) were recruited in this randomized, controlled, crossover, double-blinded trial. In a random order, subjects consumed a fully controlled diet rich in SFA (SFA: 13.4% of calories; n-6 PUFA: 4.0%) or rich in n-6 PUFA (SFA: 6.0%; n-6 PUFA: 11.3%) for periods of 4 weeks separated by a 4-week washout period. At the end of each diet, the in vivo kinetics of apoB-containing lipoproteins were measured and the intestinal expression of key genes involved in lipoprotein metabolism was assessed in duodenal biopsy samples taken from each participant.
Results: LDL apoB-100 pool size (PS) was significantly decreased after the n-6 PUFA diet compared with the SFA diet (Δ=-7.8%; P=0.005). This difference was attributed to a reduction in LDL apoB-100 production rate (PR) after the n-6 PUFA diet (Δ=-10.0%; P=0.003). There were no differences in LDL apoB-100 FCR between the two diets. Intestinal expression of genes involved in lipoprotein synthesis, namely apoB (Δ=-16.6%; P=0.005), MTP (Δ=-18.4%; P=0.006) and HNF-4α (Δ=-8.2%; P=0.008), was reduced after the n-6 PUFA diet, compared with the SFA diet.
Conclusions: In dyslipidemic and IR men, substitution of dietary SFA with n-6 PUFA reduces LDL-C concentrations primarily through reduced endogenous production of LDL apoB-100 particles. This effect is likely to be mediated, at least in part, by the downregulation of key genes involved in lipoprotein synthesis within the intestine.
Author Disclosures: J. Drouin-Chartier: None. A.J. Tremblay: None. M. Lépine: None. V. Lemelin: None. B. Lamarche: Research Grant; Modest; CIHR. Other Research Support; Modest; Atrium Innovations. P. Couture: None.
- © 2016 by American Heart Association, Inc.