Substitution of dietary ω-6 polyunsaturated fatty acids for saturated fatty acids decreases LDL apolipoprotein B-100 production rate in men with dyslipidemia associated with insulin resistance: a randomized controlled trial

Abstract

Background: The substitution of omega (ω)-6 (n-6) polyunsaturated fatty acids (PUFAs) for saturated fatty acids (SFAs) is advocated in cardiovascular disease prevention. The impact of this substitution on lipoprotein metabolism in subjects with dyslipidemia associated with insulin resistance (IR) remains unknown.

Objective: In men with dyslipidemia and IR, we evaluated the impact of substituting ω-6 PUFAs for SFAs on the in vivo kinetics of apolipoprotein (apo) B-containing lipoproteins and on the intestinal expression of key genes involved in lipoprotein metabolism.

Design: Dyslipidemic and IR men (n = 36) were recruited for this double-blind, randomized, crossover, controlled trial. Subjects consumed, in a random order, a fully controlled diet rich in SFAs (SFAs: 13.4% of energy; ω-6 PUFAs: 4.0%) and a fully controlled diet rich in ω-6 PUFAs (SFAs: 6.0%; ω-6 PUFAs: 11.3%) for periods of 4 wk, separated by a 4-wk 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 quantified in duodenal biopsies taken from each participant.

Results: The substitution of ω-6 PUFAs for SFAs had no impact on TRL apoB-48 fractional catabolic rate (Δ = -3.8%, P = 0.7) and production rate (Δ = +1.2%, P = 0.9), although it downregulated the intestinal expression of the microsomal triglyceride transfer protein (Δ = -18.4%, P = 0.006) and apoB (Δ = -16.6%, P = 0.005). The substitution of ω-6 PUFAs for SFAs decreased the LDL apoB-100 pool size (Δ = -7.8%; P = 0.005). This difference was attributed to a reduction in the LDL apoB-100 production rate after the substitution of ω-6 PUFAs for SFAs (Δ = -10.0%; P = 0.003).

Conclusions: This study demonstrates that the substitution of dietary ω-6 PUFAs for SFAs decreases the production and number of LDL particles in men with dyslipidemia and IR. This trial was registered at clinicaltrials.gov as NCT01934543.

Keywords: insulin resistance; intestinal mRNA expression; lipoprotein metabolism; omega-6 polyunsaturated fatty acids; saturated fatty acids.

© 2018 American Society for Nutrition. All rights reserved.

Figures

FIGURE 1

Flow chart of participants.

FIGURE 2

Percent changes in intestinal mRNA levels following the ω-6 PUFA diet compared with the SFA diet in men with dyslipidemia and insulin resistance (n = 30). Intestinal mRNA levels were normalized according to the expression of the house-keeping gene, TATA box binding protein, prior to statistical analyses. Values are presented as the mean change (%) ± SEM. *Significant change vs. SFA diet (P < 0.05). P values were calculated with mixed models for repeated measures with subjects as a random effect. ABC, ATP-binding casstte; ACAC, acetyl-CoA carboxylase; ACAT2, acetyl-CoA acetyltransferase 2; ACS1, acyl-CoA synthase 1; ANGPTL, angiopoietin-like; Apo, apolipoprotein; DGAT, diglyceride acyltransferase; FABP2, fatty acid-binding protein 2; FADS, fatty acid desaturase; FATP4, fatty acid transport protein 4; HMG CoAR, hydroxymethylglutaryl-CoA reductase; HNF4α, hepatocyte nuclear factor 4 α; LDLR, LDL receptor; LRP1, LDL receptor-related protein 1; MGAT-2, α-1,6-mannosyl-glycoprotein 2-β-N-acetylglucosaminyltransferase; mRNA, messenger RNA; MTP, microsomal triglyceride transfer protein; NPC1L1, Niemann-Pick C1-like 1; PCSK9, proprotein convertase subtilisin/kexin type 9; SAR1B, SAR1 gene homolog B; SCD, stearoyl-CoA desaturase; SRB, scavenger receptor class B t ype 1; SREBP2, sterol regulatory element-binding protein; VLDLR, VLDL receptor.