CHRONIC ALCOHOLISM & LIVER ENERGY & LIPID METABOLISM

我的酗酒相关研究的主要目标是 表征由以下原因导致的肝脏相关病理学 慢性酒精消耗 主要的努力将是 研究肝脏能量发生的变化 酒精诱导的早期（脂肪肝）代谢 肝脏疾病 我们之前的研究记录了几个 乙醇诱导的肝线粒体损伤。 完整 现在将研究肝细胞，以确定抑郁症是否 体外观察到的线粒体功能对线粒体功能有不利影响 肝细胞的能量状态。 实验旨在 确定1）乙醇引起的肝细胞能量变化 代谢和2）在体内功能的变化， 你好 类似的措施将实施， 中央周围和门静脉周围肝细胞，以确定是否 乙醇引起的肝脏能量代谢改变 在中央周围比门静脉周围区域更大， 小叶 这些研究应提供必要的信息， 评价乙醇诱导的中心周围缺氧 是酒精性肝病发生的一个病因 疾病 上述调查，旨在确定修改 在细胞和细胞器水平的肝脏能量代谢中， 将伴随一系列研究来调查 乙醇发挥其作用的分子机制 的结构和功能。 的影响 慢性乙醇消耗对线粒体结构的影响 由于我们已经获得证据， 无论是催化性能和亚基组成的 这种酶在乙醇喂养的大鼠中发生改变。 还将进行研究，以确定 乙醇对线粒体基因组表达的影响。 现在有 有证据表明，这些多肽编码的 线粒体基因组在肝脏中的含量较低 乙醇喂养动物的线粒体。 中描述的研究 这项建议旨在确认，这确实是 案子 实验也概述，以确定是否乙醇 消耗抑制这些多肽的生物合成， 改变转录 这些关于乙醇影响的研究 膜相关多肽将补充广泛的 目前正在进行调查，以确定 乙醇引起的对膜脂的影响和 在膜功能上。

The major objective of my alcoholism-related research is to characterize the liver associated pathology which results from chronic ethanol consumption. The major effort will be an investigation of those changes that occur in hepatic energy metabolism during the early (fatty liver) stage of ethanol-induced liver disease. Our previous studies have documented several ethanol-induced lesions in liver mitochondria. The intact hepatocyte will now be investigated to determine if the depression in mitochondrial function observed in vitro adversely affects the energy state of the liver cell. Experiments are designed to determine 1) ethanol-elicited alterations in hepatocyte energy metabolism and 2) changes in the in vivo functioning of the mitochondrion. Similar measurements will be implemented with pericentral and periportal hepatocytes to determine whether ethanol-elicited alterations in hepatic energy metabolism are greater in the pericentral than the periportal region of the lobule. These studies should provide information needed to evaluate the suggestion that ethanol-induced pericentral hypoxia is an etiological factor in development of alcohol-induced liver disease. The above investigation, which is designed to determine alterations in hepatic energy metabolism at the cellular and organelle levels, will be accompanied by a series of studies to investigate the molecular mechanism(s) by which ethanol elicits its effect(s) on the structure and function of the mitochondrion. The effect of chronic ethanol consumption on the structure of the mitochondrial ATP synthase will be determined since we have obtained evidence that both the catalytic properties and the subunit composition of this enzyme are altered in ethanol-fed rats. Studies will also be carried out to determine the effects of ethanol on expression of the mitochondrial genome. There is now evidence that suggests that those polypeptides encoded on the mitochondrial genome are present in lowered amounts in liver mitochondria from ethanol-fed animals. The studies described in this proposal are designed to confirm that this is, indeed, the case. Experiments are also outlined to determine if ethanol consumption depresses the biosynthesis of these polypeptides by altering transcription. These studies of the effects of ethanol on membrane-associated polypeptides will complement the extensive investigations currently in progress to establish the relationship between ethanol-elicited effects on membrane lipids and alterations in membrane function.