Exaggerated postprandial lipaemia has been implicated in the development of atherosclerosis. Thus, by reducing postprandial TAG concentrations, exercise may play a role in delaying atherogenic progression. This thesis sought to explore the qualitative nature of, and the mechanisms behind, the moderate exercise-induced attenuation to postprandial lipaemia. Before the experimental studies commenced, a reproducibility study was undertaken. This showed that in a group of eight middle-aged men, the postprandial plasma TAG response differed by only 1.9 ± 5.1 % (mean ± standard error) on a testretest basis, indicating that the oral fat tolerance test had enough precision to detect the effect of exercise on TAG metabolism. Previous work suggested that the exercise-induced reduction to lipaemia was linked to the energy expended by exercise. As the attenuation may have been mediated by energy deficit, rather than exercise per se, a study comparing the effect of a 90-minute moderate exercise session with an equivalent dietary-induced energy deficit on postprandial lipid metabolism was undertaken, in a group of eleven postmenopausal women. This showed that the reduction in postprandial lipaemia elicited by exercise was far greater than that elicited by intake-restriction (20 % vs. 7 %). The second experimental study aimed to establish the effect of a 90-minute moderate exercise session on postprandial chylomicron- and very-Iow-density lipoprotein (VLDL)-TAG concentrations, and its effect on exogenous (through use of a l3e-Iabelled lipid) and endogenous fat oxidation, in a group oftwelve middle-aged men. Exercise reduced postprandial lipaemia by 23 %, and over three-quarters of this reduction was due to lower VLDL-TAG concentrations. Increases in endogenous fat oxidation accounted for over half of the increase in postprandial fat oxidation. In the third experimental study, the effect of a 90-minutes moderate exercise session on Intralipid clearance, and postprandial lipaemia, was determined in a group of eight middle-aged men. Exercise attenuated postprandial lipaemia by 18 %, but did not increase Intralipid clearance. Taken together, these data imply that moderate exercise predominantly reduced postprandial TAG concentrations by reducing hepatic VLDL secretion, rather than increasing TAG clearance, and this effect is not mediated by whole-body energy deficit. In addition, this work has shown that moderate exercise is effective at attenuating postprandial lipaemia in middle-aged men and postmenopausal women.

Proprotein Convertase Subtilisin / Kexin Type-9 (PCSK9) has emerged as a major regulator of plasma cholesterol levels. PCSK9 is secreted mainly from the liver and circulates as a plasma protein. PCSK9 binds cell surface low-density lipoprotein (LDL) receptors and mediates their degradation upon endocytosis in the liver. This decreases the liver’s ability to clear LDL-cholesterol from the blood. PCSK9 is also capable of binding LDL particles themselves; this interaction inhibits the ability of PCSK9 to bind and mediate LDLR degradation in cultured hepatic cells, but its effect on PCSK9 function in vivo remains unknown. A disordered N-terminal region of the PCSK9 prodomain is necessary for binding to isolated LDL particles in vitro. This N-terminal region is also autoinhibitory to PCSK9-LDL receptor binding. We hypothesized that the N-terminal of the PCSK9 prodomain plays a role in an allosteric mechanism that regulates PCSK9 function. Through mutagenesis studies, we found that both a conserved stretch of acidic residues and an adjacent conserved stretch of hydrophobic residues are crucial for the PCSK9-LDL interaction; the hydrophobicity of the residue at position 38 (Tyr) within the conserved acidic stretch was also found to be important for this. Helical wheel modeling of the prodomain N-terminal sequence revealed the potential for a lipid-ordered amphipathic helix to form, which may aid PCSK9 docking onto LDL. Replacing residues A44 and L41 with helix-disrupting proline residues abolished LDL binding. Co-pelleting ultracentrifugation assays also show that wild-type PCSK9 is capable of associating with liposomes, while the A44P mutation disrupts this lipid association. The A44P-PCSK9 mutation, showing an 80-90% decrease in LDL association but with LDL receptor binding and degrading functions intact, may serve as an important tool in future studies investigating the PCSK9-LDL interaction in vivo. Elucidation of the mechanism by which LDL-binding naturally inhibits PCSK9 activity may also help to develop new anti-PCSK9 therapeutics in the future.

The effects of vitamin E supplementation during late gestation were evaluated in dairy or beef cattle in three experiments. Dairy cows were injected with vitamin E and selenium (Se) in one study; beef cows were offered oral vitamin E supplementation via a free-choice vitamin-mineral mix in two studies. Breed-related effects were also evaluated. Jerseys had higher blood Se and lower serum vitamin E concentrations than Holsteins at dry-off and higher blood Se concentrations than Holsteins 3-4 weeks pre-calving and at calving. Selenium supplementation increased blood Se concentrations at calving. Treatment did not affect serum vitamin E concentrations at calving or post-calving, nor blood Se concentrations post-calving. Beef cattle consuming supplemental vitamin E (treatment) had greater responses to treatment when calving in late winter than when calving in late summer. Treated multiparous cows calving in winter had increased serum and colostral vitamin E concentrations but treatment did not affect colostral or serum immunoglobulin G (IgG) concentrations of their calves. Calves from treated, multiparous cows calving in winter had increased 205-day adjusted weaning weights (AWWs). Treatment did not affect colostral vitamin E or IgG concentrations of nulliparous heifers calving in winter, nor serum vitamin E or IgG concentrations, or AWWs of their calves. Six hundred IU supplemental vitamin E/head/day did not affect serum vitamin E concentrations of dams, colostral vitamin E or IgG concentrations, serum vitamin E or IgG concentrations, or growth of calves in the summer-calving herd. Breed-related differences in vitamin E concentrations and AWW occurred in both herds. Consumption of 600-1000 IU vitamin E/cow/day (treatment) during late gestation via a free-choice vitamin-mineral mix increased vitamin E concentrations in serum and the lipoprotein fraction containing no apolipoprotein B (non-ApoB) from 1-2 weeks pre-calving to calving. Treatment group calves had higher vitamin E concentrations in serum and non-ApoB than control group calves. Treatment did not affect cholesterol or phospholipid concentrations in serum or the lipoprotein fractions of either cows or calves. Treatment increased vitamin E cholesterol (VEC) and vitamin E phospholipid (VEPL) ratios in the serum and non-ApoB of cows and calves. Various breed-related differences also occurred. / Ph. D.

No / Bacterial lipoproteins are proteins that are post-translationally modified with a diacylglyceride at an N-terminal cysteine, which serves to tether these proteins to the outer face of the plasma membrane or to the outer membrane. This paper reviews recent insights into the enzymology of bacterial lipoprotein biosynthesis and localization. Moreover, we use bioinformatic analyses of bacterial lipoprotein signal peptide features and of the key biosynthetic enzymes to consider the distribution of lipoprotein biosynthesis at the phylum level. These analyses support the important conclusion that lipoprotein biosynthesis is a fundamental pathway utilized across the domain bacteria. Moreover, with the exception of a small number of sequences likely to derive from endosymbiont genomes, the enzymes of bacterial lipoprotein biosynthesis appear unique to bacteria, making this pathway an attractive target for the development of novel antimicrobials. Whilst lipoproteins with comparable signal peptide features are encoded in the genomes of Archaea, it is clear that these lipoproteins have a distinctive biosynthetic pathway that has yet to be characterized.

Methods Three hundred thirty-nine patients (230 men, 109 women) treated with lipoprotein apheresis in Saxony, Germany, in 2018 are described in terms of age, lipid pattern, risk factors, cardiovascular events, medication, and number of new admissions since 2014, and the data are compared with figures from 2010 to 2013. Results Patients were treated by 45.5 physicians in 16 lipoprotein apheresis centers. With about 10 patients per 100 000 inhabitants, the number of patients treated with lipoprotein apheresis in Saxony is twice as high as in Germany as a whole. The median treatment time was 3 years. Almost all patients had hypertension; type 2 diabetes mellitus was seen significantly more often in patients with low Lipoprotein(a). Cardiovascular events occurred in almost all patients before initiation of lipoprotein apheresis, under apheresis therapy the cardiovascular events rate was very low in this high-risk group. For some cardiovascular regions even no events could be observed. Conclusions The importance of lipoprotein apheresis in Saxony had been increasing from 2010 to 2018.

Dissertation (Ph.D.) -- University of Texas Southwestern Medical Center at Dallas, 2008. / Vita. Bibliography: p. 135-148.

No description available.

It has been proposed that exercise may confer protection against coronary heart disease by inducing changes in plasma lipoproteins and especially high density lipoprotein (HDL) subfractions that are associated with a reduced incidence of this condition. This thesis examines the effects of different forms of exercise and dietary variation on HDL, to determine whether exercise-induced changes in HDL subfractions are consistent with their role in providing protection against coronary heart disease. No changes were observed in the concentration of low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), HDL-cholesterol (HDL-C) or HDL particle size after acute bouts of exercise. However, a significant increase in the concentration of HDL3-C and a significant decrease in HDL2-C was evident following a 21 km and a 42 km race. In a series of prolonged walks on different diets, progressive and significant increases in the concentration of HDL-C (HDL2) occurred during walking on mixed and high-fat diets. These changes were accompanied by significant reductions in the concentration of VLDL-C and increases in the particle size of HDL. In contrast, walking on a high-carbohydrate diet was followed by a significant decrease in the concentration of HDL-C and increase in the concentration of VLDL-C and VLDL-triglyceride (VLDL-TG). In the absence of exercise, a similar but less pronounced response was observed during and after the high-fat diet, whereas a greater decrease in the concentration of HDL-C occurred during the high-carbohydrate diet. Under each set of experimental conditions, changes in the proportion of apoprotein E-rich HDL, a subfraction of HDL that has been implicated in a direct mechanism of coronary protection, appeared to be unrelated to increases in HDL-C and HDL particle size. These results therefore indicated that variation in diet can profoundly influence the effects of exercise upon HDL subfractions and suggest that prolonged walking may, in part, confer health benefit through HDL facilitating the clearance of TG-rich lipoproteins.

Ultracentrifugation and imaging techniques of human blood serum are precise and information-rich methods for obtaining information about an individual’s lipoprotein particle content. The information derived from lipoprotein separations via an ultracentrifuge plays a key role in the area of preventative medicine in regards to atherosclerosis. Two of the most critical lipoprotein characteristics, diameter and density, are well preserved with the proper isopycnic gradient. Currently, lipoprotein particles are stained, ultracentrifuged, and profiled through image analysis. This particular technique is helpful in determining particle density and can be correlated loosely with particle concentration. The need to completely quantify lipoprotein concentrations is imperative in assessing risk factors accurately. Light scattering techniques, primarily Rayleigh scattering, are applied to density separated serum samples in resulting in improved qualitative data with progress in quantitative measurements through imaging alone. The Rayleigh theory dictates that a particle’s scattered intensity is based upon the incident intensity, the particle’s diameter, and the particle’s concentration when strict criteria are met within the sample and imaging apparatus. Applying this innovative imaging technique of Rayleigh scattering to ultracentrifuge tubes containing separated lipoproteins, particle concentrations at differing diameters can be calculated. This thesis primarily goes through the time consuming task of optimizing the innovative Rayleigh scattering system so that correct quantitative estimations can be performed. Constrained by Rayleigh theory and system limitations, lipoproteins of 15 nm to 35 nm are focused upon. By doing so, previously disguised data in regards to lipoprotein subclasses is exposed. Lipoprotein diameters are estimated from Rayleigh imaged serum profiles and the estimations are confirmed through secondary size analysis achieved by dynamic light scattering instrumentation. In addition to Rayleigh optimization, a strategy for quantifying the ultracentrifuged lipoprotein particles using the recently applied scattering technique is explained in detail providing a foundation for further research. In regards to all feasibility studies presented within this thesis, much success was achieved in furthering quantitation efforts in lipoprotein density profiling.

Ultracentrifugation and imaging techniques of human blood serum are precise and information-rich methods for obtaining information about an individual’s lipoprotein particle content. The information derived from lipoprotein separations via an ultracentrifuge plays a key role in the area of preventative medicine in regards to atherosclerosis. Two of the most critical lipoprotein characteristics, diameter and density, are well preserved with the proper isopycnic gradient. Currently, lipoprotein particles are stained, ultracentrifuged, and profiled through image analysis. This particular technique is helpful in determining particle density and can be correlated loosely with particle concentration. The need to completely quantify lipoprotein concentrations is imperative in assessing risk factors accurately. Light scattering techniques, primarily Rayleigh scattering, are applied to density separated serum samples in resulting in improved qualitative data with progress in quantitative measurements through imaging alone. The Rayleigh theory dictates that a particle’s scattered intensity is based upon the incident intensity, the particle’s diameter, and the particle’s concentration when strict criteria are met within the sample and imaging apparatus. Applying this innovative imaging technique of Rayleigh scattering to ultracentrifuge tubes containing separated lipoproteins, particle concentrations at differing diameters can be calculated. This thesis primarily goes through the time consuming task of optimizing the innovative Rayleigh scattering system so that correct quantitative estimations can be performed. Constrained by Rayleigh theory and system limitations, lipoproteins of 15 nm to 35 nm are focused upon. By doing so, previously disguised data in regards to lipoprotein subclasses is exposed. Lipoprotein diameters are estimated from Rayleigh imaged serum profiles and the estimations are confirmed through secondary size analysis achieved by dynamic light scattering instrumentation. In addition to Rayleigh optimization, a strategy for quantifying the ultracentrifuged lipoprotein particles using the recently applied scattering technique is explained in detail providing a foundation for further research. In regards to all feasibility studies presented within this thesis, much success was achieved in furthering quantitation efforts in lipoprotein density profiling.