Abstract 16511: Isocaloric Fructose Restriction Improves Postprandial Chylomicron and VLDL Excursions in Adolescents With Obesity by Reducing Angiopoietin-Like Protein 3 and Apolipoprotein CIII

Introduction: Delayed postprandial triglyceride-rich lipoprotein (TRL) metabolism is associated with increased atherogenic risk. Dietary fructose is a preferred lipogenic substrate which contributes to NAFLD and dyslipoproteinemia. Hypothesis: Isocaloric fructose restriction reduces postprandial TRL excursions in part by affecting the modulation of lipoprotein lipase (LPL) activity and peripheral clearance rates. Methods: We determined the effect of 9 days of isocaloric fructose restriction on fasting and postprandial TRL metabolism markers in obese Latino and African American children (9-18 years old; n=30) with high habitual sugar consumption (>50 g/d). Metabolic assessments were performed on day 0 and day 10 of isocaloric fructose restriction (starch substituted for sugar, same macronutrient composition). To follow postprandial TRL metabolism, after an initial double-sized meal, single-sized meals (providing 67% of daily calories, 15% protein, 35% fat, 50% carbohydrate) were fed every 30 minutes, with blood sampled every hour for 8 hours. Fructose content of meals reduced from 12% on day 0 to 4% on day 10. Paired t-tests compared change from day 0 to day 10 within each child. Results: Fasting TG, apoCIII, and ANGPTL3 reduced by 25%, 28% and 26% respectively (p <0.01). Postprandial AUC of TG, apoCIII, ANGPTL3, VLDL, chylomicrons (apoB48) reduced by 35%, 34%, 40%, 17%, 19% (p <0.01), while no changes were found in fasting or AUC for ANGPTL4, ANGPTL8 nor LPL mass. Conclusions: Short-term isocaloric fructose restriction improved postprandial chylomicron and VLDL metabolism in children with obesity. Specific and selective improvements in ANGPTL3 and apoCIII suggest differential modulation of LPL activity as a putative mechanism that deserves further exploration.

Lipoprotein Lipase Inhibitor, Nordihydroguaiaretic Acid, Aggravates Metabolic Phenotypes and Alters HDL Particle Size in the Western Diet-Fed db/db Mice

Lipoprotein lipase (LPL) hydrolyzes triglycerides in lipoprotein to supply fatty acids, and its deficiency leads to hypertriglyceridemia, thereby inducing metabolic syndrome (MetSyn). Nordihydroguaiaretic acid (NDGA) has been recently reported to inhibit LPL secretion by endoplasmic reticulum (ER)-Golgi redistribution. However, the role of NDGA on dyslipidemia and MetSyn remains unclear. To address this question, leptin receptor knock out (KO)-db/db mice were randomly assigned to three different groups: A normal AIN76-A diet (CON), a Western diet (WD) and a Western diet with 0.1% NDGA and an LPL inhibitor, (WD+NDGA). All mice were fed for 12 weeks. The LPL inhibition by NDGA was confirmed by measuring the systemic LPL mass and adipose LPL gene expression. We investigated whether the LPL inhibition by NDGA alters the metabolic phenotypes. NDGA led to hyperglycemia, hypertriglyceridemia, and hypercholesterolemia. More strikingly, the supplementation of NDGA increased the percentage of high density lipoprotein (HDL)small (HDL3a+3b+3c) and decreased the percentage of HDLlarge (HDL2a+2b) compared to the WD group, which indicates that LPL inhibition modulates HDL subclasses. was NDGA increased adipose inflammation but had no impact on hepatic stress signals. Taken together, these findings demonstrated that LPL inhibition by NDGA aggravates metabolic parameters and alters HDL particle size.

Platycodi Radix Beverage Reduced the Postprandial Lipemia Response to a High-fat Load in Randomized Controlled Trials of Healthy Subjects (P12-009-19)

Objectives High postprandial lipemia is a characteristic of metabolic abnormality recognized as a risk factor inducing cardiovascular disease. The objective of this study was to investigate the effects of Platycodi radix (PR) beverage on postprandial lipemia response after challenging with a high-fat/sugar load using both single-dose cross-over and 8-week repeated paralleled designs in healthy subjects. Methods A total of 52 and 96 subjects were included in the two studies, respectively. Postprandial blood samples were collected at designated time points from 0 to 6 hours after a high-fat load at each visit to determine triglyceride (TG) and lipoprotein lipase (LPL) activity and mass in plasma, chylomicron and very low-density lipoprotein (VLDL). A general linear mixed-effect model analysis of time point values and area under the curves (AUCs) was performed to estimate the effect of PR beverage on postprandial lipemia response. Results In a single-dose cross-over design study, PR beverage consumption significantly increased lipoprotein lipase mass (P = 0.011, β estimate = 4.295) and reduced TG concentration in VLDL (P = 0.038, β estimate = −52.69) at 6-hour as compared to those in placebo consumption with a high-fat load. Postprandial TG responses as measured by AUC for 6 hours were significantly correlated with a high-fat dietary score MEDFICTS in chylomicron (r = 0.276, P = 0.008) and VLDL (r = 0.213, P = 0.040). In a 8-week repeated parallel design study, postprandial lipemia responses were compared considering the interaction between group and week. PR beverage consumption decreased postprandial serum TG response (AUCn, P = 0.039; total AUC, P = 0.088). In addition, PR increased plasma LPL mass (AUCn, P = 0.076) that is a clearing factor that hydrolyzed TG of chylomicron and VLDL in the lipoprotein metabolism. Conclusions In both of single and long-term intake, PR beverage consumption improved the degradation of postprandial TG level with increasing postprandial LPL mass. However, detail LPL mechanisms of PR consumption should be further analyzed. Funding Sources This work was carried out with the support of “Cooperative Research Program for Agriculture Science & Technology Development” Rural Development Administration, Republic of Korea and the BK21 PLUS program of the Ministry of Education.

Lipoprotein lipase is active as a monomer

Lipoprotein lipase (LPL), the enzyme that hydrolyzes triglycerides in plasma lipoproteins, is assumed to be active only as a homodimer. In support of this idea, several groups have reported that the size of LPL, as measured by density gradient ultracentrifugation, is ∼110 kDa, twice the size of LPL monomers (∼55 kDa). Of note, however, in those studies the LPL had been incubated with heparin, a polyanionic substance that binds and stabilizes LPL. Here we revisited the assumption that LPL is active only as a homodimer. When freshly secreted human LPL (or purified preparations of LPL) was subjected to density gradient ultracentrifugation (in the absence of heparin), LPL mass and activity peaks exhibited the size expected of monomers (near the 66-kDa albumin standard). GPIHBP1-bound LPL also exhibited the size expected for a monomer. In the presence of heparin, LPL size increased, overlapping with a 97.2-kDa standard. We also used density gradient ultracentrifugation to characterize the LPL within the high-salt and low-salt peaks from a heparin-Sepharose column. The catalytically active LPL within the high-salt peak exhibited the size of monomers, whereas most of the inactive LPL in the low-salt peak was at the bottom of the tube (in aggregates). Consistent with those findings, the LPL in the low-salt peak, but not that in the high-salt peak, was easily detectable with single mAb sandwich ELISAs, in which LPL is captured and detected with the same antibody. We conclude that catalytically active LPL can exist in a monomeric state.

Preheparin serum lipoprotein lipase mass interacts with gender, gene polymorphism and, positively, with smoking

Correlates of preheparin serum lipoprotein lipase (LPL) mass and its associations with the likelihood of metabolic syndrome (MS) and coronary heart disease (CHD) were investigated.: A cross-sectional study was carried out in a population sample (n=352, median age 55). MS was defined according to modified Adult Treatment Panel III criteria.: Age-adjusted geometric mean preheparin LPL concentrations were 58.6±1.04 ng/mL in men and 66.9±1.03 ng/mL in women (p<0.004). A positive interaction with both the:Clin Chem Lab Med 2009;47:208–15.