Ten young adults were divided into an exercising group (n = 6) and sedentary group (n = 4). Smoking, ingestion of alcohol, drugs and oral contraceptives were prohibited during 9 weeks of study. Diets were prepared by university food service. Food consumed was recorded and nutrient intakes were assessed. Cheese was consumed in 84 to 112 gram portions every day for two separate 14 day periods. All other dairy products were prohibited in the diet except 240 ml of two percent milk per day. When cheese was consumed, daily diets contained ca 400 kcal, 100 mg cholesterol, and 700 mg calcium more than diets consumed without cheese. Individual body weights were stable and no significant changes occurred in any anthropometric measure over nine weeks. A trend of becoming more lean existed in the exercise group. However, there was no significant change in serum total cholesterol, lipids, calcium, or anthropometric measures during the study. These results seriously question the advisability of recommending restricted consumption of dairy products to lower serum cholesterol.

No description available.

Indiana University-Purdue University Indianapolis (IUPUI) / The incidence of Metabolic Syndrome (MetS) is increasing worldwide and accompanied by elevated risks for cardiovascular disease (CVD) and other subsequent comorbidities. MetS is associated with increased circulating triglycerides. A key enzyme involved in triglyceride (TG) clearance is lipoprotein lipase (LPL) whose activity is modulated by a variety of factors. Recent literature has identified the importance of angiopoietin-like proteins (ANGPTL) as regulators of LPL activity and has hypothesized a model in which three of these proteins interact with LPL to regulate the partitioning of TG metabolism from adipose to skeletal muscle. The work detailed in this dissertation adds to the model of ANGPTL regulation of LPL by establishing how ANGPTL8 modulates the ability of ANGPTL3 and ANGPTL4 to inhibit LPL activity in the bloodstream and localized environments, respectively. In the updated model, elevated insulin concentrations result in increased hepatic ANGPTL3/8 secretion and increased ANGPTL4/8 in adipose tissue. ANGPTL3/8 works as an endocrine molecule to inhibit skeletal muscle LPL from hydrolyzing circulating TG. Simultaneously, ANGPTL4/8 works in a paracrine mechanism to bind LPL on the endothelial vasculature adjacent to adipose tissue to alleviate ANGPTL4-mediated LPL inhibition and also prevent ANGPTL3/8 inhibition of localized LPL. Thus, in the postprandial state free fatty acids (FFA) from the hydrolysis of TG are directed into adipocytes for storage. Under fasting conditions, ANGPTL8 production is decreased in adipocytes and hepatocytes. This decreased production results in diminished ANGPTL4/8 and ANGPTL3/8 secretion from their respective tissues. As a result, ANGPTL4 inhibits adipocyte localized LPL activity while ANGPTL3 at physiological concentrations has minimal effect on LPL activity. Furthermore, any ANGPTL3/8 which is produced has its LPL-inhibitory ability diminished by the circulating apolipoprotein ApoA5. LPL is more active in skeletal muscle compared to adipose tissue where energy is shunted towards utilization in the muscle and away from storage in adipose tissue. A complete understanding of LPL regulation by ANGPTL proteins can potentially provide therapeutics targets for MetS.

京都大学 / 0048 / 新制・課程博士 / 博士(農学) / 甲第17905号 / 農博第2028号 / 新制||農||1018(附属図書館) / 学位論文||H25||N4801(農学部図書室) / 30725 / 京都大学大学院農学研究科応用生命科学専攻 / (主査)教授 植田 和光, 教授 加納 健司, 教授 小川 順 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DGAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20801号 / 医博第4301号 / 新制||医||1025(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 松田 道行, 教授 山下 潤, 教授 宮本 享 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(農学) / 甲第21161号 / 農博第2287号 / 新制||農||1060(附属図書館) / 学位論文||H30||N5135(農学部図書室) / 京都大学大学院農学研究科応用生命科学専攻 / (主査)教授 栗原 達夫, 教授 小川 順, 教授 阪井 康能 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DGAM

No description available.

Thesis (MSc. Medical Science (Chemical Pathology)) -- University of Limpopo, 2017 / Obesity has been associated with dyslipidaemia (increased levels of triglycerides, total cholesterol and low levels of HDL-C together with small dense lipoprotein particles) in the absence of metabolic disorders such as, type 2 diabetes mellitus and inflammation. Since community based studies in South Africa reported that obesity is more common in women, and rural Africans have a more favourable lipid profile compared to their White counterparts, the current study investigated the association of obesity in women without metabolic disorders with lipid levels and changes in proportions of small and large LDL and HDL particles. Methods The present study was part of the project “Prevention, Control and Integrated Management of Chronic Disease in a rural area, South Africa”. A total of 521 women participated in the above project. After excluding people with diabetes mellitus, insulin resistance and inflammation, 308 women were left and of these 67 were obese. Sixty seven ages matched, randomly selected non-obese women served as controls. Anthropometry variables as well as systolic and diastolic blood pressures were measured and the WHO steps questionnaire was administered to collect information on medication, lifestyle and diseases. Fasting blood levels of total cholesterol, HDL C, triglyceride, adiponectin, CRP, glucose and insulin were measured. Proportions of small and large HDL and LDL particles were determined. Results There was no significant difference in TC, TG and LDL-C levels (p=0.558, 0.087 and 0.948) between obese and non-obese women or between women with increased waist circumference (WC) and those with normal WC. The HDL-C concentration was significantly lower in obese women compared to women with non- obese (p=0.001). The lipid ratios TC/HDL-C and Apo B-100/Apo A-I were significantly higher in obese women than those with non- obese (p=0.013 and p=0.006) respectively. The same phenomenon was observed in women with xv increased waist circumference (p=0.001** and p=0.025* respectively). Adiponectin levels were significantly lower in obese women compared to non-obese women (p=0.004**) and in women with increased waist circumference compared to those with normal waist circumference (p=0.016*). The proportions of small dense HDL and LDL lipoprotein particles were similar in obese and non-obese women. Both obese and abdominally obese women had significantly higher odds ratios of low levels of HDL-C and elevated Apo B-100/Apo A-I. Adiponectin was a significant predictor of elevated TC and TG in both obese and abdominally obese women while BMI was a significant predictor of low HDL-C in obese women. Waist circumference was a significant predictor of low HDL-C in abdominally obese women. Conclusion In the current study, obesity in women was significantly associated with lipid abnormalities such as low HDL-C levels, raised lipid ratios (TC/HDL-C and Apo B 100/Apo A-I) and low levels of adiponectin, after excluding metabolic disorders / VLIR

Niacin is a highly effective, lipid regulating drug associated with a number of metabolically induced side effects such as prostaglandin (PG) mediated flushing and hepatic toxicity. In an attempt to reduce the development of these adverse effects, scientists have investigated differing methods of niacin delivery designed to control drug release and alter metabolism. However, despite successful formulation of various orally based capsule and tablet delivery systems, patient adherence to niacin therapy is still compromised by adverse events such as PG-induced flushing. While the primary advantage of orally dosed formulations is ease of use, alternative delivery options such as transdermal delivery or polymeric micro/nanoparticle encapsulation for oral administration have shown promise in niacin reformulation. However, the effectiveness of these alternative delivery options in reducing inimical effects of niacin and maintaining drug efficacy is still largely unknown and requires more in-depth investigation. In this paper, we present an overview of niacin applications, its metabolic pathways, and current drug delivery formulations. Focus is placed on oral immediate, sustained, and extended release niacin delivery as well as combined statin and/or prostaglandin antagonist niacin formulation. We also examine and discuss current findings involving transdermal niacin formulations and polymeric micro/nanoparticle encapsulated niacin delivery.

Serum amyloid A (SAA) is a small, evolutionarily well-conserved, acute-phase protein best known as the protein precursor for amyloid A amyloidosis. During acute injury, infection, or inflammation, SAA plasma concentration rapidly rises 1000-fold, but the benefit of this dramatic increase is unclear. SAA functions in the innate immune response, cell signaling, and lipid homeostasis. Most SAA circulates on plasma high-density lipoproteins (HDL), where it reroutes HDL for lipid recycling. The aim of this dissertation is to provide a structural basis for understanding SAA-lipid interactions and to elucidate the structure-function relationship in this ancient protein. SAA is an intrinsically disordered protein that acquires ~50% helical structure when bound to lipids, and is ~80% helical in three available atomic-resolution x-ray crystal structures. We took advantage of these crystal structures of lipid-free SAA to propose the binding site for various lipids, including lipids in HDL. We postulated that SAA, as a monomer, binds lipids via two amphipathic helices, h1 and h3, that form a concave hydrophobic surface, and that the curvature of this surface defines the binding preference of SAA for HDL versus larger lipoproteins. Next, we used murine SAA1.1 and a membrane-mimicking model phospholipid, palmitoyl-oleoyl phosphocholine (POPC), to reconstitute SAA-lipid complexes and characterize their overall structure, stability and stoichiometry using an array of spectroscopic, electron microscopic, and biochemical methods. We observed preferential formation of ~10 nm particles that mimic HDL size, accompanied by the α-helical folding. To probe the local protein conformation and dynamics in these SAA-POPC particles, we used hydrogen-deuterium exchange mass spectrometry. Analysis of the amount and the kinetics of deuterium uptake clearly established h1 and h3 as the lipid-binding site. Moreover, we determined that SAA binding to lipid follows a mixed model that combines induced fit, promoting α-folding in h3, with conformational selection, stabilizing pre-existing conformations in h1 and around the h2-h3 linker. Taken together, our results provided the structural basis necessary for understanding SAA-lipid interactions, which are central to beneficial functions of SAA as a housekeeping molecule, and to its misfolding in amyloid. This research sets the stage for understanding SAA interactions with its numerous other functional ligands.