Ratios between average VLDL metabolism parameters after dietary MCFA supplementation versus linoleic acid supplementation; values < 1 indicate a higher value after linoleic acid supplementation.

<p>Ratios are shown to allow comparing differences after dietary supplementation between parameters with different dimensions. * Indicates a significant difference in two-way ANOVA between MCFA and linoleic acid supplementation, with p<0.05. The first three parameters have dimensions <i>volume/# particles</i>, the uptake and lipolysis measure have the dimension <i>1/time</i>, and the production measure has dimension <i># particles/(volume * time)</i>. Differences in VLDL triglyceride and cholesterol pool size can be found in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0100376#pone-0100376-t002" target="_blank">table 2</a>. The p-values of the significant measures are: uptake/production in VLDL (p = 0.030); VLDL performance (p = 0.040); VLDL lipolysis (p = 0,0213); VLDL uptake (p = 0.0135).</p

Schematic model of the compartmental model used for apolipoprotein B-100 (apoB) kinetic analysis.

<p>The assembly of lipoprotein is modeled by 9-compartment delay for apoB. The plasma apoB kinetic is modeled by a single hydrolysis step. Only a single VLDL lipoprotein fraction is considered, consisting of the VLDL1 and VLDL2 fractions in Adiels et al <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0100376#pone.0100376-Adiels1" target="_blank">[29]</a>. The free leucine plasma kinetics is modeled by two pools (3 and 4) and a plasma compartment (1), which interchange materials with an intracellular compartment (2). Compartment 2 feeds the apoB synthetic machinery.</p

Baseline characteristics of the 12 male subjects (mean ± sd).

<p>^*BMI  =  Body Mass Index: is the ratio between the body weight (kg) and the square of the height in meters of a person and is a (healthy) weight index.</p><p><i>^**</i>Dutch Eating Behavior Questionnaire for assessment of restrained, emotional, and external eating behavior.</p

Dietary Medium Chain Fatty Acid Supplementation Leads to Reduced VLDL Lipolysis and Uptake Rates in Comparison to Linoleic Acid Supplementation

<div><p>Dietary medium chain fatty acids (MCFA) and linoleic acid follow different metabolic routes, and linoleic acid activates PPAR receptors. Both these mechanisms may modify lipoprotein and fatty acid metabolism after dietary intervention. Our objective was to investigate how dietary MCFA and linoleic acid supplementation and body fat distribution affect the fasting lipoprotein subclass profile, lipoprotein kinetics, and postprandial fatty acid kinetics. In a randomized double blind cross-over trial, 12 male subjects (age 51±7 years; BMI 28.5±0.8 kg/m²), were divided into 2 groups according to waist-hip ratio. They were supplemented with 60 grams/day MCFA (mainly C8:0, C10:0) or linoleic acid for three weeks, with a wash-out period of six weeks in between. Lipoprotein subclasses were measured using HPLC. Lipoprotein and fatty acid metabolism were studied using a combination of several stable isotope tracers. Lipoprotein and tracer data were analyzed using computational modeling. Lipoprotein subclass concentrations in the VLDL and LDL range were significantly higher after MCFA than after linoleic acid intervention. In addition, LDL subclass concentrations were higher in lower body obese individuals. Differences in VLDL metabolism were found to occur in lipoprotein lipolysis and uptake, not production; MCFAs were elongated intensively, in contrast to linoleic acid. Dietary MCFA supplementation led to a less favorable lipoprotein profile than linoleic acid supplementation. These differences were not due to elevated VLDL production, but rather to lower lipolysis and uptake rates.</p></div

Ratios between average hepatic hipase (HL) lipolysis activity and total lipolysis activity (which also includes LPL-related lipolysis) averaged over all particles from VLDL to LDL that are included in the model, after dietary MCFA supplementation versus linoleic acid supplementation.

<p>* Indicates a significant difference in two-way ANOVA between MCFA and linoleic acid supplementation, with p<0.05 (p = 0.047).</p

HPLC lipoprotein measurements after both treatments, analyzed by two-way ANOVA for treatment and waist-hip-ratio differences (mean ± sd).

<p>HPLC lipoprotein measurements after both treatments, analyzed by two-way ANOVA for treatment and waist-hip-ratio differences (mean ± sd).</p

Ratios between average IDL and LDL metabolism parameters after dietary MCFA supplementation versus linoleic acid supplementation.

<p>LDL performance is the average of the two ratios shown to the sides. “fl/particle” is the unit of all three ratios. * Indicates a significant difference in two-way ANOVA between MCFA and linoleic acid supplementation, with p<0.05. p-values of the significant measures are: uptake/influx in IDL and LDL (p = 0.011); LDL performance (p = 0.010).</p

Ratios between average IDL and LDL metabolism parameters in lower body obese (LBO) versus upper body obese (UBO) subjects.

<p>LDL performance is the average of the two ratios shown to the sides. “fl/particle” is the unit of all three ratios. * Indicates a significant difference in two-way ANOVA between LBO and UBO subjects, with p<0.05. p-values of the significant measures are: uptake/influx in IDL and LDL (p = 0.012); LDL performance (p = 0.009).</p

Average lipoprotein cholesterol profiles, including chylomicrons through LDL, a: after dietary MCFA (black line) and linoleic acid (grey line) supplementation and b: for lower body obese (black line) and upper body obese (grey line) supplementation.

<p>* Significant difference in two-way ANOVA between dietary supplementations with p<0.05. P-value of significant changes (from left to right, subscript indicates lipoprotein diameter) in panel a: p₆₄ = 0.0804; p₅₄ = 0.0072; p₄₅<0.0001; p₃₇<0.0007; p₃₁ = 0.0319; p₂₉ = 0.0211; p₂₆ = 0.0108; p₂₃ = 0.0141; p₂₁ = 0.0179; p₁₉ = 0.0125; p₁₇ = 0.0098. P-value of significant changes (from left to right, subscript indicates lipoprotein diameter) in panel b: p₂₆ = 0.0412; p₂₃ = 0.0112;p₂₁ = 0.0115;p₁₉ = 0.0103;p₁₇ = 0.0115.</p

Effects on some lipid parameters of SUB885C and existing drugs in the ApoE^*3Leiden.CETP female mice model.

<p>Basic diet for ApoE*3Leiden.CETP female mice during run-in and study period: Western type diet with 15% w/w fat plus different content of cholesterol.</p><p>NS: no significance.</p><p>*Dependent on different doses of Niacin.</p