Fatty Liver Disease and Hepatic Energy Homostatis in SH*

SH* 中的脂肪肝疾病和肝能量稳态

• 批准号: 6619448
• 负责人: JEANNE M CLARK
• 金额: $ 41.59万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-15 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6619448
• 关键词: African American; behavior therapy; bioenergetics; biopsy; body physical activity; body temperature; clinical research; epidemiology; fatigue; fatty liver; homeostasis; human subject; human therapy evaluation; hunger; ketone body; liver disorder; liver metabolism; longitudinal human study; magnetic resonance imaging; male; nuclear magnetic resonance spectroscopy; nutrient intake activity; obesity; outcomes research; questionnaires; weight loss

DESCRIPTION (provided by applicant): Obesity is associated with insulin resistance, diabetes mellitus, hypertension, and dyslipidemia; less well known is its association with non-alcoholic fatty liver disease (NAFLD). The prevalence of NAFLD is 14-21 percent in some populations, is more common in those who are diabetic or over age 45, and can lead to fibrosis and cirrhosis. Recent evidence indicates that NAFLD is a consequence of disordered hepatic energy homeostasis. Several emerging lines of evidence suggest the overall hypothesis that disordered hepatic energy homeostasis and subsequent NAFLD may play a central role in mediating the adverse metabolic effects of obesity and may influence the success of weight loss interventions. Unfortunately, prior clinical studies have been limited. We, therefore, have the following specific hypotheses: 1) NAFLD and disordered hepatic energy homeostasis will be common in SHOW participants; 2) NAFLD will be associated with disordered energy homeostasis, African-American race and male gender; 3) disordered hepatic energy homeostasis will be associated with a proinflammatory state, and adaptive decreases in normal energy requirements; 4) those with disordered hepatic energy homeostasis will have a weaker response to the SHOW intervention compared to those with normal hepatic energy homeostasis; and 5) the SHOW intervention will improve NAFLD and hepatic energy homeostasis in those with little or no defect in hepatic energy homeostasis but worsen it in those with moderate to severe defects. To test these hypotheses we propose a single center ancillary study to the SHOW trial. The study sample for the ancillary study would be the 313 SHOW participants enrolled at Johns Hopkins. We will measure symptoms of hunger and fatigue (0, 6, 12 mo.) and collect additional data including liver enzymes (0, 6, 12 mo.), MRI Spectroscopy (0, 12 mo.), and ketone bodies, insulin levels, and proinflammatory cytokines (0, 12 mo.) The main outcomes will be the prevalence, correlation, and 1-year progression of NAFLD and disordered hepatic energy homeostasis. Our secondary outcomes will be weight change, physical activity, dietary intake, and symptoms of hunger and fatigue in those with and without NAFLD and disordered hepatic energy homeostasis. If our hypotheses are confirmed, this study will establish blood and other clinical markers of NAFLD and disordered hepatic energy homeostasis, which will facilitate population based research; advance our understanding of the pathophysiology of NAFLD; establish disordered hepatic energy homeostasis as a biologic modifier of behavioral approaches to weight loss; and determine whether weight loss improves NAFLD or poses unsuspected risks.

描述（由申请人提供）： 肥胖与胰岛素抵抗，糖尿病，高血压，高血压有关 和血脂异常；鲜为人知的是它与非酒精脂肪的关联 肝病（NAFLD）。 NAFLD的患病率在某些人中为14-21％ 种群在糖尿病患者或45岁以上的人中更常见，并且可以 导致纤维化和肝硬化。最近的证据表明NAFLD是 肝能量稳态无序的结果。几条新兴线 有证据表明肝脏能量无序的总体假设 体内平衡和随后的NAFLD可能在调解核心方面发挥核心作用 肥胖的不良代谢作用，可能会影响体重的成功 损失干预措施。不幸的是，先前的临床研究受到限制。 因此，我们有以下特定假设：1）NAFLD和无序 肝能量稳态在表演参与者中很常见； 2）NAFLD会 与能量稳态无关，非裔美国人种族和 男性； 3）无序的肝能量稳态将与 正常能量需求的促炎状态和自适应降低； 4） 那些肝脏能量稳态无序的人对 与肝脏能量正常稳态的表演干预相比； 5）表演干预将改善NAFLD和肝脏能量稳态 在那些在肝能量稳态中几乎没有或没有缺陷的人中，但使它恶化 在中度至重度缺陷的人中。为了检验这些假设，我们提出了 单一中心辅助研究进行表演试验。研究样本 辅助研究将是约翰·霍普金斯（Johns Hopkins）入学的313个表演。 我们将测量饥饿和疲劳的症状（0，6，12 mo。）并收集 其他数据在内，包括肝酶（0、6、12 mo。），MRI光谱（0，12 mo。）和酮体，胰岛素水平和促炎细胞因子（0，12 Mo。）主要结果将是患病率，相关性和1年 NAFLD和无序的肝能量稳态的进展。我们的次要 结局将是体重改变，体育锻炼，饮食摄入和症状 有或没有NAFLD和无序肝的饥饿和疲劳 能量稳态。如果确认我们的假设，这项研究将建立 NAFLD的血液和其他临床标记和肝功能无序的标记 稳态，这将促进基于人群的研究；推进我们的 了解NAFLD的病理生理学；建立无序的肝 能量稳态作为重量行为方法的生物学修饰符 损失;并确定减肥是否改善了NAFLD或毫无疑问 风险。