REGULATORY MECHANISMS IN LIPID METABOLISM

拟议研究的持续目标是描述和 了解调节血管紧张素转换的生化和生理机制 肝脏对游离脂肪酸(FFA)的代谢。我们建议研究 极低密度与甘油三酯分泌的相互关系 脂蛋白(VLDL)，FFA的氧化(酮的生成和二氧化碳的产生)， 脂肪生成和甘油脂合成、胆固醇生成和肝脏 脂肪变性。灌流的大鼠肝脏和分离的肝细胞将用于 研究肝脏对游离脂肪酸代谢的替代途径。这些研究 体外实验将与极低密度脂蛋白甘油三酯分泌率和 对完整动物极低密度脂蛋白利用率的估计。我们将继续 研究肝脏分泌的内分泌依赖调节， 极低密度脂蛋白的组成和性质，以及相关的替代途径 游离脂肪酸的代谢。甲状腺状况、肾上腺皮质激素、 性腺类固醇、胰高血糖素、儿茶酚胺和环核苷酸 学习。我们计划研究钙离子作为一种 甘油脂微粒体合成的调节剂及其可能的作用 肝脂代谢中正常作用的介体。我们计划继续 为了研究底物(FFA)对肝脏分泌的依赖调节， 极低密度脂蛋白的组成和性质。我们将继续调查 肝脏分泌的一种特定极低密度脂蛋白的各种特性是如何 体外对特定的FFA或混合物的反应，影响随后的 极低密度脂蛋白的肝外利用。利用率将通过以下方式进行评估 脂蛋白脂酶活性的体外测定及血浆测定 体内半衰期(T1/2)。我们将研究它们之间的相互关系 极低密度脂蛋白与胆固醇生成和胆固醇的输出调节 酯化(分别激活HMG-CoA还原酶和LCAT)。 饮食、内分泌疾病和疾病对血浆脂蛋白的影响 部分原因肯定是肝脏对游离脂肪酸的代谢发生了变化。 了解这些机制是本研究的目的。

The continuing objectives of the proposed research are to describe and understand the biochemical and physiological mechanisms which regulate the metabolism of free fatty acids (FFA) by the liver. We propose to study the interrelationships among secretion oftriglyceride and the very low density lipoprotein (VLDL), oxidation of FFA (ketogenesis and CO2 production), lipogenesis and glycerolipid synthesis, cholesterogenesis, and hepatic steatosis. The perfused rat liver and isolated hepatocytes will be used to study alternate pathways of metabolism of FFA by the liver. These studies in vitro will be correlated with VLDL triglyceride secretion rate and estimation of VLDL utilization in the intact animal. We will continue to investigate the endocrine-dependent regulation of hepatic secretion, composition, and properties of the VLDL, and related alternate pathways of metabolism of FFA. The effect of thyroidal status, adrenoglucocorticoids, gonadal steroids, glucagon, catecholamines, and cyclic nucleotides will be studied. We plan to investigate the role of calcium (Ca++) ion as a regulator of the microsomal synthesis of glycerolipids and as a possible mediator of hormal action in hepatic lipid metabolism. We plan to continue to study the substrate (FFA)-dependent regulation of hepatic secretion, composition, and properties of the VLDL. We will continue to investigate how the various properties of a specific VLDL secreted by the liver in vitro in response to a specific FFA or mixture, affect the subsequent extra-hepatic utilization of that VLDL. Utilization will be evaluated by activity of lipoprotein lipase in vitro, and by measurement of plasma half-life (T1/2) in vivo. We will studdy the interrelationships among regulation of output the VLDL and cholesterogenesis and cholesterol esterification (activation of HMG-CoA reductase and LCAT, respectively). The effects of diet, endocrinopathies and disease on plasma lipoproteins must, in part, result from altered metabolism of FFA by the liver. Understanding of these mechanisms is the purpose of this study.