NUTRITIONAL EFFECTS OF SUGARS ON LIVER LIPIDS

糖对肝脂的营养影响

• 批准号: 3354678
• 负责人: CHARLES Edward SPARKS
• 金额: $ 15.72万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1991-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3354678
• 关键词: apolipoproteins; atherosclerosis; blood lipoprotein; cholesterol; dietary carbohydrates; glucose; hormone regulation /control mechanism; hyperlipoproteinemia; immunochemistry; insulin; laboratory mouse; laboratory rabbit; liver cells; liver metabolism; monoclonal antibody; monosaccharides; nutrition related tag; radiotracer; sucrose

Monosaccharides and disaccharides are known to result in hyperlipoproteinemia in rabbit nutritional studies. In rabbits fed semi-purified diets, sucrose as a carbohydrate source results in hyperlipoproteinemia in excess of that of dietary glucose or fructose. In the sucrose model significant hypercholesterolemia and hypertriglyceridemia occur followed by early atherosclerotic changes in ten to twenty weeks. In these rabbits the hyperlipoproteinemia is of endogenous origin as marked by the apo B variant, apo BH, of hepatic origin. Full characterization in the rabbit model of hyperlipoproteinemia in the absence of exogenous cholesterol is important considering proposals to substitute carbohydrate for fat in human diets. We propose to study effects of dietary sucrose or constituent monosaccharides, fructose or glucose on plasma lipoproteins over a twenty week period including tolerance of sugars following acute administration. In vivo studies will be complemented by rabbit hepatocyte studies of lipoprotein synthesis and secretion using radionuclide incorporation studies of lipids, apolipoproteins, and phosphorylated forms of apo B. Primary hepatocyte studies will characterize the acute regulation by insulin of lipoprotein synthesis and secretion using media containing fructose and/or glucose, fatty acids and various hormones (glucagon and dexamethasone). The effect of insulin on degree of apo B phosphorylation will be studied. These studies will further previous hepatocyte experiments in a model where only apo BH is secreted. Monoclonal antibodies to rabbit apolipoproteins will be used in the quantitation of apolipoproteins, immunoaffinity isolation of subpopulations of lipoproteins and immunochemical identification of lipoproteins that contain multiple epitopes. Particle composition of various lipoprotein fractions with respect to lipids and apolipoprotein composition and particle heterogeneity will be determined by epitope specific immunoaffinity isolation. The rabbit model is important to develop as it closely approximates the human in terms of endogenous apo B secretion and its ability to be studied in terms of atherogenesis. Particle composition of apo B and apo A-I lipoproteins is seen as critical to the cholesterol balance in the arterial wall and particle composition is well known to be critical in hepatic and peripheral clearance of lipoproteins. Studies are important considering apo B and apo A-I lipoproteins are risk factors in atherogenesis.

已知单糖和二糖导致 家兔高脂蛋白血症的营养研究。 家兔 半纯化的饮食，蔗糖作为碳水化合物来源， 高脂蛋白血症超过膳食葡萄糖，或 果糖。 在蔗糖模型中， 和高甘油三酯血症发生后，早期动脉粥样硬化 在十到二十周内发生变化。 在这些兔子中， 高脂蛋白血症是内源性的，其标志是载脂蛋白 肝源性B变体，载脂蛋白BH。 完整的特性描述， 兔高脂蛋白血症模型 胆固醇是重要的考虑建议， 碳水化合物代替脂肪。 我们建议研究 膳食蔗糖或组成单糖，果糖或 葡萄糖对血浆脂蛋白的影响 包括急性给药后糖的耐受性。 在 体内研究将通过兔肝细胞研究补充， 使用放射性核素的脂蛋白合成和分泌 脂质、载脂蛋白和脂质的掺入研究 apo B的磷酸化形式。 原代肝细胞研究将 胰岛素对脂蛋白的急性调节作用 使用含有果糖和/或 葡萄糖、脂肪酸和各种激素（胰高血糖素和 地塞米松）。 胰岛素对载脂蛋白B水平的影响 将研究磷酸化。 这些研究将进一步 先前的肝细胞实验中，只有载脂蛋白BH的模型， 秘密的 兔载脂蛋白的单克隆抗体将 用于定量载脂蛋白、免疫亲和性 脂蛋白亚群的分离和免疫化学 鉴定含有多个表位的脂蛋白。 各种脂蛋白组分的颗粒组成， 涉及脂质和载脂蛋白组合物和颗粒 异质性将由表位特异性 免疫亲和分离。 兔子模型的重要性在于， 在内源性载脂蛋白B分泌方面与人类接近 以及它在动脉粥样硬化形成方面的研究能力。 颗粒 载脂蛋白B和载脂蛋白A-I脂蛋白的组成被认为是 动脉壁和颗粒中的胆固醇平衡 众所周知，组合物在肝脏和外周中是关键的。 清除脂蛋白。 研究是重要的考虑载脂蛋白 脂蛋白B和载脂蛋白A-I是动脉粥样硬化形成的危险因素。