Zhengling Li

Change in LDL particle size is associated with change in plasma triglyceride concentration.

Low density lipoprotein (LDL) particle size is inversely associated with plasma triglyceride concentration in cross-sectional analyses. In the present study, changes in the LDL particle size of 227 participants of the Framingham Offspring Study were analyzed longitudinally by nondenaturing gradient gel electrophoresis at two examinations that were separated by 3-4 years. All subjects had triglyceride concentrations < 400 mg/dl at both exams. Using laser scanning densitometry to assess mean LDL particle size, 56% of samples displayed a change in size: 41% had a one-band size change, 13% had a two-band change, and 2% had a three-band change. These changes in size corresponded to a 15% change in pattern type, based on pattern A and B terminology. There was a significant inverse association between change in LDL size and change in triglyceride (p < 0.0001) and glucose (p < 0.004) concentrations, body weight (p < 0.02), and age (p < 0.03). There was also a significant positive association with change in high density lipoprotein (HDL) cholesterol concentration (p < 0.0001). Change in LDL cholesterol concentration, as calculated by use of the Friedewald formula, however, showed no significant association with change in LDL size (p < 0.9). There was also no significant association with change in smoking or blood pressure, but there was a nonsignificant inverse trend associated with alcohol intake (p < 0.08).(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of a National Cholesterol Education Program Step 2 Diet in Normolipidemic and Hypercholesterolemic Middle-Aged and Elderly Men and Women

We tested the effects of a National Cholesterol Education Program (NCEP) Step 2 diet (30% of calories or less as total fat, less than 7% saturated fat, and less than 200 mg cholesterol per day) on plasma lipid levels in normocholesterolemic and hypercholesterolemic middle-aged and elderly men and women. Thirty-two subjects were studied. Eight normolipidemic subjects (6 men and 2 women, mean age 56 +/- 13 years) with LDL cholesterol levels of less than 4.14 mmol/L (160 mg/dL) were given a baseline diet similar in composition to the diet currently consumed in the United States (35% of calories as total fat and 14% as saturated fat, with 147 mg cholesterol per 1000 kcal) for 6 weeks. Subjects were then placed on an NCEP Step 2 diet (26% total fat, 4% saturated fat, 45 mg cholesterol per 1000 kcal) for 24 weeks. In addition, 24 subjects (12 men and 12 women, mean age 62 +/- 12 years) with moderate hypercholesterolemia (LDL cholesterol levels of 4.14 mmol/L or above) were given a baseline diet for 6 weeks and then the NCEP Step 2 diet for 6 weeks. Energy intakes were adjusted to keep body weight constant throughout the study. In both normolipidemic and hypercholesterolemic subjects, consumption of the NCEP Step 2 diet was associated with significant changes in levels of total cholesterol (-20% and -16%, respectively), LDL cholesterol (-21% and -18%, respectively), and HDL cholesterol (-16% and -15%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary Restriction of Saturated Fat and Cholesterol Decreases HDL ApoA-I Secretion

We examined the mechanisms responsible for the decrease in HDL cholesterol (HDL-C) levels after the consumption of a diet low in total fat, saturated fat, and cholesterol. Twenty-one subjects with a mean age of 58+/-12 years were placed on a baseline isocaloric diet (15% protein, 49% carbohydrate, 36% fat, and 150 mg/1000 kcals of cholesterol) and then switched to an NCEP Step 2 diet (15% protein, 60% carbohydrate, 25% fat, and 45 mg/1000 kcals of cholesterol). After 6 or 24 weeks on each diet, subjects received a 15-hour primed-constant infusion of [5,5,5-2H3]-L-leucine. HDL apoA-I and apoA-II tracer curves were determined by gas chromatography-mass spectrometry and fitted to a monoexponential equation. Compared with the baseline diet, consumption of the Step 2 diet lowered HDL-C mean levels by 15% (1.03+/-0.23 to 0.88+/-0.16 mmol/L, P<0.001), apoA-I by 12% (1.25+/-0.15 to 1.10+/-0.13 g/L, P<0. 001) and the TC/HDL-C ratio by 5% (0.145+/-0.04 to 0.137+/-0.03). No significant changes were observed in apoA-II levels and HDL particle size with diet. HDL apoA-I fractional catabolic rate did not change (0.219+/-0.052 to 0.220+/-0.043 pools/day, P=0.91) but HDL apoA-I secretion rate decreased by 8% (12.26+/-3.07 to 10.84+/-2.11 mg. kg-1. day-1, P=0.03) during consumption of the Step 2 diet. There was no effect of diet on apoA-II fractional catabolic rate or secretion rate. Our results indicate that the decrease in HDL-C and apoA-I levels during the isocaloric consumption of a Step 2 diet paralleled the reductions in apoA-I secretion rate.

Impact of hydrogenated fat consumption on endogenous cholesterol synthesis and susceptibility of low-density lipoprotein to oxidation in moderately hypercholesterolemic individuals☆☆☆

The effects of replacing corn oil with corn oil margarine in stick form on endogenous cholesterol synthesis and susceptibility of low-density lipoprotein (LDL) to oxidation were assessed in 14 middle-aged and elderly men and women aged 63 +/- 12 years (mean +/- SD) with moderate hypercholesterolemia (mean LDL-cholesterol [LDL-C], 4.24 +/- 0.59 mmol/L at the time of recruitment). Subjects consumed each of two diets for 32-day periods, one enriched in corn oil, which contained 30% of energy as fat (7% saturated fatty acid [SFA], 9% monounsaturated fatty acid [MUFA] [0.4% 18:1n9 trans], and 11% polyunsaturated fatty acid [PUFA]) and 85 mg cholesterol/4.2 MJ, and one enriched in stick corn oil margarine, which contained 30% fat (8% SFA, 12% MUFA [4.2% 18:1n9trans], and 8% PUFA) and 77 mg cholesterol/4.2 MJ. Both diets were isocaloric and supplied by a metabolic research kitchen. Mean total cholesterol levels were lowest (P = .039) when subjects consumed the corn oil-enriched diet (5.01 +/- 0.51 mmol/L) as compared with the margarine-enriched diet (5.30 +/- 0.58 mmol/L). LDL-C levels were 3.24 +/- 0.51 and 3.50 +/- 0.54 mmol/L when subjects consumed corn oil-and margarine-enriched diets, respectively (P = .058). There were no significant differences in high-density lipoprotein cholesterol (HDL-C) or triglyceride concentrations between the two experimental periods. Consumption of the margarine-enriched diet versus the corn oil-enriched diet tended to result in lower cholesterol fractional synthetic rates ([C-FSRs] 0.0466 +/- 0.0175 and 0.0668 +/- 0.0298, respectively, P = .080) and cholesterol absolute synthetic rates ([C-ASRs] 1.1761 +/- 0.5375 and 1.6954 +/- 0.8685, respectively, P = .092); however, differences did not reach statistical significance. Consumption of the margarine-enriched diet versus the corn oil-enriched diet resulted in a significantly higher concentration of alpha-tocopherol in both plasma and LDL(P = .004 and P = .011, respectively). LDL particle size tended to be smaller after subjects consumed the margarine-enriched diet versus the corn oil-enriched diet (P = .103). Susceptibility of LDL to oxidation was similar after consumption of the corn oil- and margarine-enriched diets. These data suggest that an increased rate of endogenous cholesterol synthesis did not contribute to the higher plasma cholesterol concentrations during the period when subjects consumed the margarine-enriched diet. Therefore, the increase in cholesterol concentration resulting from margarine consumption was likely attributable, at least in part, to a decreased catabolic rate of cholesterol. Additionally, susceptibility of LDL to in vitro oxidation was not altered by consumption of hydrogenated fat.

Apolipoprotein A-I and A-II Kinetic Parameters as Assessed by Endogenous Labeling With [2H3]Leucine in Middle-Aged and Elderly Men and Women

The purpose of our study was to investigate high density lipoprotein (HDL) apolipoprotein (apo) A-I and apoA-II kinetics in a state of constant feeding after a primed-constant infusion of [5,5, 5-(2)H(3)]L-leucine in 32 normolipidemic older men and postmenopausal women (aged 41 to 79 years). ApoA-I and apoA-II were isolated from plasma HDL, and enrichment was determined by gas chromatography/mass spectrometry. The fractional secretion rate was obtained by using a monoexponential equation calculated with the SAAM II program (Department of Bioengineering, University of Washington, Seattle). Mean HDL cholesterol (HDL-C) and total triglyceride levels were 23% higher and 27% lower, respectively, in women than in men. Mean plasma apoA-I levels were 10% greater in women than in men, whereas mean apoA-II levels were similar. HDL size, estimated by gradient-sizing gels and by the HDL-C/apoA-I+apoA-II ratio, was significantly higher in women than in men. Mean apoA-I secretion rates (SRs) were similar in men and women (12.28+/-3.64 versus 11.96+/-2.92 mg/kg per day), whereas there was a trend toward a lower (-13%) apoA-I fractional catabolic rate (FCR) in women compared with men (0.199+/-0.037 versus 0. 225+/-0.062 pools per day, P=0.11). Mean apoA-II SRs (2.21+/-0.57 versus 2.27+/-0.91 mg/kg per day) and FCRs (0.179+/-0.034 versus 0. 181+/-0.068 pools per day) were similar in men and women. For the group as a whole, there was an inverse association between the HDL-C/apoA-I+apoA-II ratio and apoA-I FCR and between the ratio and triglyceride levels. Plasma levels of apoA-I and apoA-II were correlated with their respective SRs but not FCRs. These data suggest a major role for apoA-I and apoA-II SRs in regulating the plasma levels of these proteins, whereas apoA-I FCR might be an important factor contributing to the differences in apoA-I levels between men and postmenopausal women. Moreover, plasma triglyceride levels are important determinants of HDL size and apoA-I catabolism.

Dietary cholesterol increases the susceptibility of low density lipoprotein to oxidative modification

Evidence suggests that oxidative modification of low density lipoprotein (LDL) occurs in vivo, increasing the atherogenecity of the particle. A total of 13 subjects (age range 46-78 years) with an LDL cholesterol concentration >3.36 mmol/l consumed each of four diets for 32-day periods. The diets contained 30% energy as fat of which 2/3 was either corn oil or beef tallow with and without 115 mg/4.2 MJ of supplemental cholesterol in the form of cooked egg yolk. The susceptibility of LDL to oxidation was assessed during a challenge with hemin and hydrogen peroxide, and results are expressed as lag time to oxidation in minutes. Addition of moderate amounts of cholesterol to either the corn oil or beef tallow enriched diet resulted in increased susceptibility of LDL to oxidation (decreased lag time): 69+/-22 min versus 96+/-24 min in the corn oil diet with versus without supplemental cholesterol, respectively, P = 0.006; 82+/-20 min versus 96+/-26 min in the beef tallow diet with versus without supplemental cholesterol, respectively, P = 0.025. A stepwise equation indicated that as plasma oleic acid concentrations increased and/or linoleic acid concentrations decreased, lag time increased (decreased susceptibility to oxidation), whereas as dietary cholesterol concentrations increased, lag time decreased (increased susceptibility to oxidation). In conclusion, these data suggest that addition of a moderate amount of dietary cholesterol to a reduced fat diet rich in polyunsaturated or saturated fatty acids increased the in vitro susceptibility of LDL to oxidation.

The effect of quality and amount of dietary fat on the susceptibility of low density lipoprotein to oxidation in subjects with impaired glucose tolerance

Objectives: We examined the effects of a high fat diet rich in monounsaturated fat (MUFA-diet) and a moderate fat diet rich in polyunsaturated fat (PUFA-diet) on the susceptibility of LDL to oxidation.Subjects: 29 subjects with impaired glucose tolerance.Methods: After consuming a run-in diet [37% of energy (E%) fat, 18 E% saturated fat] for three weeks, subjects were randomly assigned either to a MUFA-diet (40 E% fat, 19 E% monounsaturated fatty acids) or a PUFA-diet (34 E% fat, 10 E% polyunsaturated fat) for eight weeks. The susceptibility of LDL to oxidation was measured by challenging LDL with hemin and H2O2 and measuring the time for the reaction to reach maximum velocity. Results are expressed as lag time to oxidation in minutes.Results: In the PUFA-diet group (n=15) lag time tended to decrease during the experimental diet (97±28 vs 90±25 min, mean±s.d., P=0.073), whereas in the MUFA-diet group (n=14) there was no significant change (lag time 96±24 vs 100±16 min, P=0.408). The mean change in lag time was −7±14 min (−7.2%) in the PUFA-diet group and +4±16 min (+4.0%) in the MUFA-diet group (P=0.029, PUFA-diet group vs MUFA-diet group). The α-tocopherol concentration in LDL increased significantly (P<0.01) in both diet groups relative to the run-in diet period, but LDL particle score did not change in either of the diet groups during the dietary intervention.Conclusions: In subjects with impaired glucose tolerance a PUFA-rich diet with a moderate amount of fat tended to increase the susceptibility of LDL to oxidation as compared to a higher fat diet rich in MUFA. Furthermore, the negative mean change in lag time to oxidation found in the PUFA-diet group differed significantly from the slightly positive mean change found in the MUFA-diet group.Sponsorship: Supported by the Foundation for Nutrition Research, Helsinki, Finland; the Council for Health Sciences, Academy of Finland, and the Ministry of Education, Finland, and the Van den Bergh Foods and Valio Ltd, Finland, for supplying the fat products for the study