Ingrid Frey

Structure of human low-density lipoprotein subfractions determined by X-ray small-angle scattering

The structure of low-density lipoprotein (LDL) particles from three different density ranges (LDL-1: d = 1.006-1.031 g/ml; LDL-3: d = 1.034-1.037 g/ml; LDL-6: d = 1.044-1.063 g/ml) was determined by X-ray small-angle scattering. By using a theoretical particle model, which accounted for the polydispersity of the samples, we were able to obtain fits of the scattering intensity that were inside the noise interval of the measured intensity. The assumption of deviations from radial symmetry is not supported by our data. This implies a spread-out conformation of the apolipoprotein B (apoB) molecule, which appears to be localized in the outer surface shell. A globular structure is not consistent with our data. Furthermore, different models exist concerning the structure of the cholesterol ester core below the phase transition temperature. The electron density data suggest an arrangement in which the steroid moieties are localized at average radii of 3.2 and 6.4 nm. Model calculations show that packing problems can only be avoided if approximately half of the acyl chains of each shell are pointing towards the center of the particle, the other half towards the surface. This arrangement of the acyl chains has never been proposed before. The LDL particles of different density classes differ mainly with respect to the size of the core but also with respect to the width of the surface shells. Model calculations show that the size of different LDL particles can be accurately predicted from the compositional data.

Physical Activity and Lipoprotein Lipid Disorders

SummaryWorking muscle plays a central role in the control of lipid metabolism. Increased physical activity induces a number of positive changes in the metabolism of lipoproteins: serum triglycerides are lowered by the increased lipolytic activity and the production of native high density lipoprotein (HDL) particles is increased. The increased lecithin: cholesterol acyltransferase activity leads to an increased production of HDL2, which in addition is catabolised more slowly due to a decreased activity of hepatic lipase. The 3 effects explain the increased HDL levels of endurance trained individuals. These effects have been demonstrated in cross-sectional as well as longitudinal studies by different groups, and can be induced by training, independent of changes in body weight. The influence of endurance activity on the quality and quantity of low density lipoprotein (LDL) particles is a further reason for the antiatherogenic potential of increased physical activity. It has been shown by several groups that small dense LDL particles represent a particular risk factor for atherosclerosis. Recent studies presented strong evidence that LDL level and composition can be influenced favourably by physical activity. In addition to the direct influence of physical activity on lipids and lipoproteins, physical exercise may improve the disturbances of haemorheological factors, particularly those associated with hypertriglyceridaemia.In conclusion, there is increased evidence that physical activity is able to favourably influence all 3 components of the atherogenic lipoprotein phenotype: the HDL concentration increases, the concentration of small dense LDL decreases, and serum triglycerides are reduced.

Effect of a weight loss intervention on anthropometric measures and metabolic risk factors in pre- versus postmenopausal women

BackgroundThe present study examines changes in body weight, fat mass, metabolic and hormonal parameters in overweight and obese pre- and postmenopausal women who participated in a weight loss intervention.MethodsSeventy-two subjects were included in the analysis of this single arm study (premenopausal: 22 women, age 43.7 ± 6.4 years, BMI 31.0 ± 2.4 kg/m2; postmenopausal: 50 women, age 58.2 ± 5.1 years, BMI 32.9 ± 3.7 kg/m2). Weight reduction was achieved by the use of a meal replacement and fat-reduced diet. In addition, from week 6 to 24 participants attended a guided exercise program. Body composition was analyzed with the Bod Pod®. Blood pressures were taken at every visit and blood was collected at baseline and closeout of the study to evaluate lipids, insulin, cortisol and leptin levels.ResultsBMI, fat mass, waist circumference, systolic blood pressure, triglycerides, glucose, leptin and cortisol were higher in the postmenopausal women at baseline.Both groups achieved a substantial and comparable weight loss (pre- vs. postmenopausal: 6.7 ± 4.9 vs 6.7 ± 4.4 kg; n.s.). However, in contrast to premenopausal women, weight loss in postmenopausal women was exclusively due to a reduction of fat mass (-5.3 ± 5.1 vs -6.6 ± 4.1 kg; p < 0.01). In premenopausal women 21% of weight loss was attributed to a reduction in lean body mass.Blood pressure, triglycerides, HDL-cholesterol, and glucose improved significantly only in postmenopausal women whereas total cholesterol and LDL-cholesterol were lowered significantly in both groups.ConclusionBoth groups showed comparable weight loss and in postmenopausal women weight loss was associated with a pronounced improvement in metabolic risk factors thereby reducing the prevalence of metabolic syndrome.

Effect of meal replacement on metabolic risk factors in overweight and obese subjects.

Aim: Our objective was to assess alterations in metabolic risk factors, body weight, fat mass and hormonal parameters following 6 weeks of lifestyle intervention with increased physical activity and either a meal-replacement regimen or a low calorie diet. Research Methods and Procedures: 90 overweight or obese subjects (age 47 ± 7.5 years, weight 90.6 ± 11.3 kg, BMI 31.5 ± 2.3) were included in this randomized controlled clinical trial. Subjects in the fat-restricted low-calorie-diet group (LCD-G; n = 30) received 2 dietary counseling sessions and instructions on how to increase physical activity. Subjects in the meal-replacement-diet group (MRD-G; n = 60) received the same lifestyle education and were instructed to replace 2 daily meals by a low-calorie high soy-protein drink. Results: Subjects in the MRD-G lost significantly more weight (6.4 vs. 3.1 kg, p < 0.01) and fat mass (5.1 vs. 2.8 kg, p < 0.01) than the LCD-G. Most metabolic risk parameters were reduced in both the MRD-G and the LCD-G; however, subjects in the MRD-G showed a higher reduction in waist circumference (6.1 vs. 1.8 cm, p < 0.01) and a larger decrease in triglycerides (–19.6 vs. +12.5 mg/dl, p < 0.01). The prevalence of the metabolic syndrome was reduced in subjects in the MRD-G only (–12%, p < 0.05) compared to an unchanged risk score in the LCD-G. The reductions in leptin (18.2 vs. 6.97 ng/ml) and insulin (4.92 vs. 0.58 µU/ml) were only significant in the MRD-G (p < 0.01). Discussion: Our data suggest that even over a short period of time, a meal-replacement diet is more effective in reducing metabolic risk factors, insulin, and leptin, and in improving anthropometric measures than a fat-restricted low-calorie diet.

Two-Year Follow-Up of an Interdisciplinary Cognitive-Behavioral Intervention Program for Obese Adults

ABSTRACT Intervention programs for treating adiposity which focus on dietary change and physical exercise often do not lead to the desired long-term reduction in weight. This article reports on the effectiveness of M.O.B.I.L.I.S., a standardized theory-driven intervention program. Participants are taught cognitive-behavioral strategies of goal setting, action planning, barrier management, and self-monitoring. Persons with obesity (N = 316) responded to a public advertisement to participate in the intervention program (IG) or comparison group (CG; quasi-experimental design). Assessments were conducted at four time points, with the last assessment being conducted two years after baseline. At the 24-month follow-up, the IG showed weight loss of 5.57%, whereas the CG lost 1.12% of their weight (t1–t4, p < .01). The results yielded significant interaction terms (group × time), indicating that the intervention had a substantial effect on food choice and level of physical exercise (p < .01). The IG showed significantly enhanced self-efficacy, stronger goal intentions, and more detailed implementation intentions than the CG at follow-ups. The intervention program has the potential to evoke enduring changes in the cognitions we hypothesized to be responsible for inducing obese adults to begin and continue regular exercise and healthy eating behavior, resulting in substantial weight loss.

Influence of acute maximal exercise on lecithin: cholesterol acyltransferase activity in healthy adults of differing aerobic performance

SummaryTo document the possible influence of a single episode of maximal aerobic stress on the serum lecithin: cholesterol acyltransferase (LCAT) activity in subjects with differing histories of training, two groups of healthy male adults [controls (C),n = 18, 28.6 years, SD 5.2, 50.1 ml · kg−1 · min−1 maximal O2 uptake (VO2max), SD 5.3; endurance trained athletes (T),n = 18, 31.4 years, SD 8.8, 65.0 ml · kg−1 · min−1VO2max, SD 2.8] were examined in a maximal aerobic stress test. In addition to the routine assessment of lipid status, LCAT activity was measured immediately before and after exercise. At rest nearly identical LCAT activity values were found in both groups: C 64.4 nmol · ml−1 · h−1, SD 16.7 vs T 65.0 nmol · ml−1 · h−1, SD 20.9. The post-exercise LCAT values induced by the maximal stress test increased significantly to (C) 95.7 nmol · ml−1 · h−1, SD 23.5, +48.6%,P<0.001; (T) 83.5 nmol · ml−1 · h−1, SD 24.3, +29.1%,P<0.01. Neither the pre nor the post-exercise individual LCAT activity values showed any significant correlation to the corresponding data on physical performance.

Low-resolution data analysis for low-density lipoprotein particle

The knowledge of the molecular structure of LDL, a large lipoprotein complex, is of great interest for medical investigations. Currently available LDL crystals do not diffract to high resolution and do not allow the application of standard crystallographic techniques. Additional difficulties arise because of a very dense crystal packing and the presence of several components with quite different mean densities. Several ab initio phasing methods previously reported by the authors have been successfully applied to find a crystallographic image of LDL at a resolution of 27 A. The most promising results have been obtained using direct phasing with a connectivity analysis of the electron-density maps. The current image makes it possible to discern a single particle covered by a layer of relatively high density that is asymmetrically distributed on the particle surface. It shows a partition of high and low densities inside the particle and, in particular, strips of varying density in the lipid core.

Relationship between obesity and concentration and composition of low-density lipoprotein subfractions in normoinsulinemic men.

Obesity, insulin resistance (IR) with hyperinsulinemia, and a dyslipoproteinemia characterized by reduced high-density lipoprotein 2 (HDL2) cholesterol and elevated levels of small, dense low-density lipoprotein (LDL) particles are risk factors for coronary artery disease (CAD). The impact of obesity independent of hyperinsulinemia on the concentration and composition of small, dense LDL subfractions is uncertain. The aim of this study was to investigate the relationship between obesity indices, namely body mass index (BMI), skinfold measurements (SF), and waist to hip ratio (WHR), and LDL-subfraction particle concentration and composition in 200 healthy men without evidence of IR. A precise analysis of the concentration of lipids and apolipoproteins and the composition of very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and two HDL- and six LDL-subfraction particles was obtained using the technique of density-gradient ultracentrifugation. Dividing the individuals according to BMI showed that those with a BMI greater than 27 kg/m2 had significantly lower HDL2 cholesterol and apolipoprotein (apo) A-I and higher VLDL and IDL cholesterol and apo B concentrations than those with a BMI less than 25 kg/m2. Regarding LDL particles, we found that men with a BMI above 25 kg/m2 had significantly more small, dense LDL particles (d 1.044 to 1.063 g/mL) and correspondingly fewer medium, dense LDL particles (d 1.031 to 1.037 g/mL) than leaner men; those with a BMI above 27 kg/m2 had the highest concentration of circulating small, dense LDL particles. These findings were not influenced by fasting insulin concentrations, IR, or WHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute and delayed effects of prolonged exercise on serum lipoproteins

SummaryTo investigate the effects of a single period of prolonged exercise on lipoprotein concentration and composition, the serum of 13 healthy, endurance trained men was examined before and after (1 h, 20 h) a field test [running time, 130 (SD 7.4) min]. We found changes in composition of all of the lipoprotein fractions isolated. In detail, all very low density lipoprotein particle components were reduced after exercise; the most pronounced changes found were in the concentrations of phospholipids (PL) and triglycerides (TG) (PL, before vs 20 h after,P<0.01; TG, before vs 20 h after,P<0.01). The serum high density lipoprotein (HDL)-cholesterol mass was unchanged after exercise, but both HDL subfractions showed changes in composition. In HDL3 the relative amounts of cholesterol increased (unesterified free cholesterol; FC) before vs 20h after,P<0.05; cholesterylester (CE), before vs 20 h after,P<0.01) and TG and PL decreased (TG and PL, before vs 20 h after,P<0.05). The HDL2 particles became enriched in the relative amount of CE (before vs 20 h after,P<0.01) and lost TG after exercise (before vs 20 h after,P<0.01). The observation that all the changes in lipoprotein concentration and composition reached their maximal differences compared to the pre-exercise values 20 h afterwards would support the assumption that circulating lipoproteins play an important role in the regeneration period, refilling the intramuscular triglyceride stores.

Apolipoprotein profile in healthy males and its relation to maximum aerobic capacity (MAC)

In order to document possible variations of apolipoproteins in relation to the maximum aerobic capacity, 36 healthy young males of different aerobic performance were examined and the serum concentrations of apolipoprotein A-I, A-II, B, C-II, C-III, E investigated. In contrast to all other lipoproteins, significant differences between the endurance-trained and control subjects could be found in the apo A-I concentrations only (1025 +/- 92 vs 1456 +/- 179 mg/l, p less than 0.001). In addition, the apolipoprotein A-II, B, C-II, C-III, E concentrations correlated neither with the maximum aerobic capacity values nor with the relative body weight of the subjects.