Substitution of dietary monounsaturated fatty acids from olive oil for saturated fatty acids from lard increases low-density lipoprotein apolipoprotein B-100 fractional catabolic rate in subjects with dyslipidemia associated with insulin resistance: a randomized controlled trial

Abstract

Background: The substitution of monounsaturated acids (MUFAs) for saturated fatty acids (SFAs) is recommended for cardiovascular disease prevention but its impact on lipoprotein metabolism in subjects with dyslipidemia associated with insulin resistance (IR) remains largely unknown.

Objectives: This study aimed to evaluate the impact of substituting MUFAs for SFAs on the in vivo kinetics of apolipoprotein (apo)B-containing lipoproteins and on the plasma lipidomic profile in adults with IR-induced dyslipidemia.

Methods: Males and females with dyslipidemia associated with IR (n = 18) were recruited for this crossover double-blind randomized controlled trial. Subjects consumed, in random order, a diet rich in SFAs (SFAs: 13.4%E; MUFAs: 14.4%E) and a diet rich in MUFAs (SFAs: 7.1%E; MUFAs: 20.7%E) in fully controlled feeding conditions for periods of 4 wk each, separated by a 4-wk washout. At the end of each diet, fasting plasma samples were taken together with measurements of the in vivo kinetics of apoB-containing lipoproteins.

Results: Substituting MUFAs for SFAs had no impact on triglyceride-rich lipoprotein apoB-48 fractional catabolic rate (FCR) (Δ = -8.9%, P = 0.4) and production rate (Δ = 0.0%, P = 0.9), although it decreased very low-density lipoprotein apoB-100 pool size (PS) (Δ = -22.5%; P = 0.01). This substitution also reduced low-density lipoprotein cholesterol (LDL-C) (Δ = -7.0%; P = 0.01), non-high-density lipoprotein cholesterol (Δ = -2.5%; P = 0.04), and LDL apoB-100 PS (Δ = -6.0%; P = 0.05). These differences were partially attributed to an increase in LDL apoB-100 FCR (Δ = +1.6%; P = 0.05). The MUFA diet showed reduced sphingolipid concentrations and elevated glycerophospholipid levels compared with the SFA diet.

Conclusions: This study demonstrated that substituting dietary MUFAs for SFAs decreases LDL-C levels and LDL PS by increasing LDL apoB-100 FCR and results in an overall improved plasma lipidomic profile in individuals with IR-induced lipidemia.

Trial registration: This trial was registered as clinicaltrials.gov as NCT03872349.

Keywords: insulin resistance; lipidomics; lipoprotein metabolism; monounsaturated fatty acids; saturated fatty acids.

FIGURE 1

Flowchart of participants.

FIGURE 2

Bar graph representing the concentrations of total LDL particles after each diet (Box A) and the percentage of sdLDL after each diet (Box B). Differences in values after the MUFA diet compared with the SFA diet are expressed in percentages. P values were calculated with a Wilcoxon signed-rank test for repeated measurements. sdLDL, small dense low-density lipoprotein.

FIGURE 3

Box plot diagram representing the standardized concentrations of the 8 most prevalent lipid classes identified from fasting plasma samples taken at the end of each diet. Concentrations of LPC, PC, and DG were higher after the MUFA diet compared with the SFA diet, whereas the latter presented elevated SM and TG concentrations. Cer, LPE, and PE showed no significant difference between the 2 diets. Boxes contain the second and third quartiles of data with the horizontal line inside them representing the median value; whiskers represent the range. Linked points represent the values of individual participants at the end of each diet. Significant P values ≤ 0.05 are shown for each lipid class. P values were calculated with a Wilcoxon signed-rank test for repeated measurements. Cer: ceramide, DG, diglyceride; LPC: lysophosphatidylcholine. LPE, lysophosphatidylethanolamine; NS, nonsignificant; PC, phosphatidylcholine; PE, phosphatidylethanolamine; SM, sphingomyelin; TG, triglyceride.

FIGURE 4

Graphical summary of the proposed mechanism explaining the cholesterol-lowering effects of substituting MUFAs for SFAs. Reduced SFA intakes downregulate sphingolipid hepatic de novo synthesis by limiting palmitate availability, resulting in lower intracellular SM and DG together with elevated PC. The ensuing reduced SM:PC ratio in circulating apoB-100-containing lipoproteins enhances LDLR activity that increases LDL uptake resulting in lowered LDL-C and non-HDL-C. LPL activity is also increased, resulting in lower circulating TG. Reduced SM content in HDL increases LCAT activity, therefore elevating circulating LPC, which is the other product of HDL-C esterification. apo, apolipoprotein; DG, diglyceride; FCR, fractional catabolic rate; LPC, lysophosphatidylcholine; PC, phosphatidylcholine; PS, pool size; SM, sphingomyelin; SMase, sphingomyelinase; SMS, sphingomyelin synthase; SPT, serine palmitoyl transferase; TG, triglyceride.