Effect of Dietary Macronutrient Composition and Weight Loss on Liver Substrate Me

膳食常量营养素成分和减肥对肝脏底物的影响

• 批准号: 7501355
• 负责人: ELIZABETH JANE PARKS
• 金额: $ 44.71万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7501355
• 关键词: Address; Adipose tissue; Affect; African American; Automobile Driving; Biopsy Specimen; Body Weight decreased; Body mass index; Caloric Restriction; Carbohydrates; Caucasians; Caucasoid Race; Clinical Chemistry; Clinical Research; Clinical Trials; Condition; Deposition; Development; Diabetes Mellitus; Diet; Dietary Carbohydrates; Dietary Fats; Dietary Fatty Acid; Dietary intake; Disease; Disease regression; Eating; Ethnic group; Fat-Restricted Diet; Fatty Acids; Fatty Liver; Fatty acid glycerol esters; Fibrosis; Future; Glucose; Goals; Health; Hepatic; Hispanics; Imaging technology; Inflammation; Insulin; Insulin Resistance; Invasive; Ketone Bodies; Ketones; Lipids; Lipoproteins; Liver; Liver Fibrosis; Liver Function Tests; Liver diseases; Macronutrients Nutrition; Mass Fragmentography; Measurement; Measures; Metabolic; Metabolism; Methodology; Methods; Monitor; NMR Spectroscopy; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Oxidative Stress; Pathway interactions; Patients; Peripheral; Plasma; Population; Prevalence; Process; Randomized; Rate; Relative (related person); Risk Factors; Serological; Source; Steatohepatitis; Testing; Time; Tissues; Treatment Efficacy; Triglycerides; United States; Woman; base; carbohydrate metabolism; design; dietary restriction; ethnic difference; fatty acid metabolism; fibrogenesis; improved; in vivo; insulin sensitivity; lipid biosynthesis; lipid metabolism; men; non-alcoholic; non-alcoholic fatty liver; nonalcoholic steatohepatitis; oxidation; response; stable isotope

Non-alcoholic steatohepatitis (NASH) is a condition characterized by elevated liver triglyceride (TG), liver damage, and inflammation in the setting of obesity, insulin resistance, and type 2 diabetes. We have previously identified and quantified the sources of excess TG found in the liver in NASH patients as deriving from the plasma FFA pool, newly-synthesized fatty acids from dietary carbohydrate (CHO), and dietary fat that entered the liver postprandially. Further, we have found significant ethnic differences in the prevalence of hepatic steatosis, with African Americans being protected relative to Caucasians and Hispanics. Clinical studies have shown that weight loss can reduce hepatosteatosis, improve liver function tests, and reduce liver fibrosis in NASH. A clinical trial will be conducted to compare the therapeutic efficacy of two different, energy-restricted diets (low-CHO and low-fat). Obese, hyperinsulinemic men and women (12 Hispanics and 12 African Americans with NASH) will be randomized to consume one of the two diets to produce a 6% weight loss over a 5-mo period. Before and after weight loss, we will determine the relative effects of these diets on hepatic-TG content and inflammation using non-invasive imaging technologies, histological assessment of liver biopsy specimens, and clinical chemistry. Stable isotopes, along with gas chromatography/ mass spectrometry and nuclear magnetic resonance spectroscopy, will be used to characterize and compare the metabolic effects of the two diets in the ethnic groups. This study represents the first time these two methodologies have been used simultaneously to assess in vivo metabolism. The study is designed to test the following hypotheses: H1, Weight reduction due to energy restriction, regardless of dietary macronutrient composition, will reduce liver-TG content; H2, Compared to a low-fat diet, a low-CHO diet will markedly reduce inflammation coincident with greater improvements in insulin sensitivity; H3, Differences in hepatic insulin resistance, lipogenesis, and/or dietary fatty acid flux between SMI-matched Hispanics and African Americans will explain the impact of dietary CHO restriction to regress liver fat. By discovering the inter-relationships between hepatic glucose and lipid metabolism in NASH, a better understanding of the metabolic mechanisms causing NASH will be gained, with the goal of more effective treatment strategies for obesity and diabetes-related liver disease in the future.

非酒精性脂肪性肝炎（NASH）是一种特征在于升高的肝脏甘油三酯（TG）、肝脏甘油三酯（TG）水平和肝脏甘油三酯（TG）水平的病症。 在肥胖、胰岛素抵抗和2型糖尿病的背景下，损伤和炎症。我们有 先前确定并量化了NASH患者肝脏中发现的过量TG的来源， 来自血浆FFA库、来自膳食碳水化合物（CHO）的新合成脂肪酸和膳食脂肪 在餐后进入肝脏此外，我们还发现，在患病率方面存在显著的种族差异。 非裔美国人相对于白种人和西班牙裔人受到保护。临床 研究表明，减肥可以减少脂肪肝，改善肝功能检查， NASH肝纤维化将进行临床试验以比较两种不同的治疗效果， 能量限制饮食（低CHO和低脂）。肥胖、高胰岛素血症的男性和女性（12名西班牙裔和 12名患有NASH的非洲裔美国人）将被随机分配到两种饮食中的一种，以产生6%的 5个月内体重减轻。减肥前后，我们将确定这些的相对影响， 饮食对肝脏TG含量和炎症的影响，使用非侵入性成像技术，组织学 肝活检标本的评估和临床化学。稳定同位素，沿着气相色谱法/ 质谱和核磁共振光谱，将用于表征和 比较两种饮食对不同种族人群代谢的影响。这项研究首次 这两种方法已被同时用于评估体内代谢。这项研究是 设计用于检验以下假设：H1，由于能量限制导致的体重减轻，无论 膳食中大量营养素的组成，将降低肝脏TG含量; H2，与低脂饮食相比，低CHO 饮食将显著减少炎症，同时胰岛素敏感性得到更大的改善; H3， SMI匹配的肝胰岛素抵抗、脂肪生成和/或膳食脂肪酸通量在 西班牙裔和非洲裔美国人将解释饮食CHO限制对肝脏脂肪消退的影响。通过 发现NASH中肝脏葡萄糖和脂质代谢之间的相互关系， 将获得对导致NASH的代谢机制的理解，目标是更有效地 未来肥胖和糖尿病相关肝病的治疗策略。