NONALCOHOLIC STEATOHEPATITIS (NASH): IS LEPTIN AN ETIOLOGICAL FACTOR (PHASE2)

非酒精性脂肪性肝炎 (NASH)：瘦素是病因吗（第 2 阶段）

• 批准号: 7603811
• 负责人: Elif Arioglu Oral
• 金额: $ 0.16万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7603811
• 关键词: Adipocytes; Blood; Blood Glucose; Body Composition; Body Size; Body fat; Characteristics; Cholesterol; Cicatrix; Computer Retrieval of Information on Scientific Projects Database; Condition; Deposition; Development; Disease; Engineering; Fatty acid glycerol esters; Funding; Grant; Hormones; Injection of therapeutic agent; Institution; Insulin; Insulin Resistance; Learning; Leptin; Liver; Liver diseases; Metabolic; Obesity; Overweight; Patients; Pattern; Persons; Phase; Population; Process; Range; Research; Research Personnel; Resistance; Resources; Skin; Source; Subgroup; United States National Institutes of Health; Weight; aged; improved; liver biopsy; liver function; male; nonalcoholic steatohepatitis

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Nonalcoholic steatohepatitis (or NASH) is known to be caused by deposition of fat in the liver and development of scarring as a consequence of fat deposition. This condition occurs more frequently in overweight and obese persons. It is often associated with resistance to the actions of insulin hormone, the primary hormone regulating blood sugar in the body. Fat cells secrete a hormone called leptin. In recent years, we have learned that obese or overweight persons make too much leptin. Having too much leptin in the blood may contribute to insulin resistance. Paradoxically, patients who do not have any fat cells also have insulin resistance. In these patients, the resistance to the actions of insulin is caused by the absence of leptin and leptin replacement significantly improves insulin resistance and fat deposition in the liver. In an earlier study, we determined the leptin levels in patients with nonalcoholic steatohepatitis and how these levels are related to body fat levels as well as responsiveness to insulin. We saw that a subgroup of patients with NASH have relatively low levels of leptin in contrast to the amount of body fat they had. We now would like to see if restoring leptin levels to normal will improve the disease process in these patients. We will now study those patients in whom we have seen low levels of leptin. Our study patients will be male patients, aged between 18 and 65 (inclusive), who do not have any other cause for their liver disease. We have put some restrictions in body size such that a spectrum of patients from normal weight to obese range would be included. They will also demonstrate low leptin levels (levels similar to only 25 % of normal population). We will use genetically engineered form of leptin manufactured by Amgen Inc. Leptin will be given via injections under the skin. We plan to continue therapy for a period of one year and evaluate the change in liver disease by a liver biopsy. We will also follow the metabolic parameters (e.g. blood cholesterol, liver function, insulin resistance) and body composition characteristics (e.g. the pattern of fat distribution in the body) that we studied in our earlier study which we called Phase 1. We expect that patients with low blood leptin levels will show improvement in their liver disease and insulin resistance when their blood leptin levels are restored to normal. '

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 已知非酒精性脂肪性肝炎（或NASH）是由肝脏中的脂肪沉积和脂肪沉积导致的瘢痕形成引起的。这种情况更常见于超重和肥胖的人。它通常与对胰岛素激素作用的抵抗有关，胰岛素激素是调节体内血糖的主要激素。脂肪细胞分泌一种叫做瘦素的激素。近年来，我们了解到肥胖或超重的人产生过多的瘦素。血液中有太多的瘦素可能会导致胰岛素抵抗。奇怪的是，没有任何脂肪细胞的患者也有胰岛素抵抗。在这些患者中，对胰岛素作用的抵抗是由缺乏瘦素引起的，瘦素替代显著改善了胰岛素抵抗和肝脏中的脂肪沉积。在早期的研究中，我们确定了非酒精性脂肪性肝炎患者的瘦素水平，以及这些水平与体脂水平以及对胰岛素的反应性的关系。我们发现，NASH患者亚组的瘦素水平相对较低，与他们的体脂量相比。我们现在想看看是否恢复瘦素水平正常将改善这些患者的疾病进程。我们现在将研究那些瘦素水平低的患者。我们的研究患者将是年龄在18 - 65岁（含）之间的男性患者，他们没有任何其他肝病原因。我们对体型进行了一些限制，以便纳入从正常体重到肥胖范围的患者。他们也将表现出低瘦素水平（水平类似于正常人群的仅25%）。 我们将使用基因工程形式的瘦素生产的安进公司。瘦素将通过皮下注射给药。 我们计划继续治疗一年，并通过肝活检评估肝脏疾病的变化。我们还将跟踪我们在早期研究中研究的代谢参数（例如血液胆固醇、肝功能、胰岛素抵抗）和身体组成特征（例如体内脂肪分布模式），我们称之为第1阶段。我们预期，当血液瘦素水平恢复正常时，血液瘦素水平低的患者将显示其肝脏疾病和胰岛素抵抗的改善。 '