NUTRITIONAL EFFECTS OF SUGARS ON LIVER LIPIDS

已知单糖和双糖可导致 兔营养研究中的高脂蛋白血症。在喂食的兔子中 半纯净饮食，蔗糖作为碳水化合物来源导致 高脂蛋白血症超过饮食中的葡萄糖或 果糖。在蔗糖模型中，显著的高胆固醇血症 高甘油三酯血症继之以早期动脉粥样硬化 在十到二十周内发生变化。在这些兔子身上， 高脂蛋白血症是内源性的，以载脂蛋白原为标志 B变异体，apo BH，起源于肝脏。中的完整角色。 无外源性高脂蛋白血症兔模型 考虑到替代胆固醇的建议，胆固醇是重要的 人类饮食中脂肪的碳水化合物。我们建议研究影响 饮食中的蔗糖或组成单糖、果糖或 20周内血糖对血浆脂蛋白的影响 包括急性给药后对糖的耐受性。在……里面 活体研究将得到兔肝细胞研究的补充 利用放射性核素合成和分泌脂蛋白 脂类、载脂蛋白和 载脂蛋白B的磷酸化形式初级肝细胞研究将 胰岛素对脂蛋白的急性调节作用特征 利用含有果糖和/或 葡萄糖、脂肪酸和各种激素(高血糖素和 地塞米松)。胰岛素对载脂蛋白B水平的影响 将对磷酸化进行研究。这些研究将进一步 先前在只有载脂蛋白BH的模型中的肝细胞实验 秘而不宣。兔载脂蛋白的单抗将是 用于载脂蛋白的定量，免疫亲和力 脂蛋白亚群的分离及免疫化学研究 鉴定含有多个表位的脂蛋白。 不同脂蛋白组份的颗粒组成 对脂类和载脂蛋白成分及颗粒的影响 异质性将由表位特异性决定。 免疫亲和分离。 兔模型的发展非常重要，因为它与 在内源性载脂蛋白B分泌方面与人类相似 以及它在动脉粥样硬化形成方面的研究能力。粒子 载脂蛋白B和载脂蛋白A-I的组成被认为是 动脉壁和颗粒中的胆固醇平衡 众所周知，肝脏和外周的成分是至关重要的。 清除脂蛋白。考虑到载脂蛋白原，研究是重要的 B和载脂蛋白A-I是动脉粥样硬化形成的危险因素。

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.