NONALCOHOLIC STEATOHEPATITIS (NASH): IS LEPTIN AN ETIOLOGICAL FACTOR (PHASE 1)

非酒精性脂肪性肝炎 (NASH)：瘦素是病因吗（第一阶段）

• 批准号: 7376578
• 负责人: Elif Arioglu Oral
• 金额: $ 0.2万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-05 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7376578
• 关键词: fat body; fats; insulin sensitivity /resistance; leptin; liver; scars

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. Being overweight impairs the action of the insulin hormone, the primary hormone responsible from controlling sugar levels in the body. This is called a state of insulin resistance. Insulin resistance is commonly seen in patients who have fat accumulation in their liver. About 10% of patients with fat accumulation in their liver develop scarring that can lead to failure of liver and death. Another factor that has been shown in research studies to play a role in preventing fat accumulation in the liver is the leptin hormone, a hormone secreted by the fat cells. Previously we have observed very low leptin hormone concentrations in an unusual group of patients with abnormal body fat. In this group, there was marked fat accumulation and scarring in the liver as well as very severe insulin resistance. Both the liver problem and the insulin resistance remarkably reversed when we administered leptin hormone and achieved near normal leptin levels in these patients for about 4 months. These results made us wonder whether leptin hormone plays a role in the fat accumulation and scarring process in other patients with this condition. However, knowledge about the variation of leptin hormone levels and body composition and how these relate to each other and insulin resistance is lacking. In this study, we would like to determine the variation in body fat distribution and blood chemistry in patients known to have fat accumulation and scarring in their liver. We also would like to know how blood chemistry and body fat distribution in these patients affect the circulating leptin concentrations. This study comprises of one day of testing that involves baseline blood work, imaging studies that help to determine body fat distribution and a test that lasts three hours to determine how effective insulin is working in the cells. We will perform these studies on 50 patients with known fat accumulation and scarring. We will use this information to determine if we can develop new therapies to reverse or slow down fat accumulation and scarring in the liver.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。超重会损害胰岛素激素的作用，胰岛素激素是控制体内血糖水平的主要激素。这就是所谓的胰岛素抵抗状态。胰岛素抵抗常见于肝脏脂肪堆积的患者。大约10%的肝脏脂肪堆积的患者会形成疤痕，导致肝脏衰竭和死亡。另一个在研究中被证明在防止肝脏脂肪堆积中起作用的因素是瘦素激素，一种由脂肪细胞分泌的激素。以前，我们观察到非常低的瘦素激素浓度在一个不寻常的一组患者异常体脂肪。在这一组中，肝脏中有明显的脂肪积累和疤痕，以及非常严重的胰岛素抵抗。当我们给予瘦素激素并使这些患者的瘦素水平接近正常水平约4个月时，肝脏问题和胰岛素抵抗都显著逆转。这些结果让我们想知道瘦素激素是否在其他患有这种疾病的患者的脂肪积累和瘢痕形成过程中发挥作用。然而，缺乏关于瘦素激素水平和身体组成的变化以及它们如何相互关联和胰岛素抵抗的知识。在这项研究中，我们想确定已知肝脏有脂肪堆积和瘢痕形成的患者体内脂肪分布和血液化学的变化。我们还想知道这些患者的血液化学和体脂分布如何影响循环瘦素浓度。这项研究包括一天的测试，包括基线血液工作，有助于确定体脂分布的成像研究，以及持续三个小时的测试，以确定胰岛素在细胞中的有效性。我们将对50名已知有脂肪堆积和瘢痕形成的患者进行这些研究。我们将利用这些信息来确定我们是否可以开发新的疗法来逆转或减缓肝脏中的脂肪积累和瘢痕形成。