REGULATORY MECHANISMS IN LIPID METABOLISM

拟议研究的持续目标是描述和 了解调节生物化学和生理机制， 肝脏对游离脂肪酸（FFA）的代谢。 我们建议研究 甘油三酯分泌与极低密度脂蛋白的关系 脂蛋白（VLDL），FFA氧化（生酮和CO2生成）， 脂肪生成和甘油脂合成、胆固醇生成和肝脏 脂肪变性 灌注的大鼠肝脏和分离的肝细胞将用于 研究肝脏代谢FFA的替代途径。 这些研究 将与VLDL甘油三酯分泌速率相关， 完整动物中VLDL利用的估计。 我们将继续 研究肝脏分泌的内分泌依赖性调节， VLDL的组成和性质，以及VLDL的相关替代途径， FFA代谢。 甲状腺状态，肾上腺糖皮质激素， 性腺类固醇、胰高血糖素、儿茶酚胺和环核苷酸将被 研究了 我们计划研究钙（Ca++）离子作为一种 调节剂的微粒体合成的甘油脂，并作为一种可能的 肝脏脂质代谢中激素作用介质。 我们计划继续 为了研究肝分泌的底物（FFA）依赖性调节， VLDL的组成和性质。 我们将继续调查 如何由肝脏分泌的特定VLDL的各种特性， 在体外响应特定FFA或混合物，影响随后的 VLDL肝外利用。 利用率将由以下人员进行评估： 脂蛋白脂酶的体外活性，并通过测量血浆 体内半衰期（T1/2）。 我们将研究它们之间的相互关系。 调节输出极低密度脂蛋白和胆固醇生成和胆固醇 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 一定部分是由肝脏FFA代谢改变引起的。 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.