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

非酒精性脂肪性肝炎(NASH)是一种以肝脏甘油三酯(TG)、肝脏 在肥胖、胰岛素抵抗和2型糖尿病的背景下，损害和炎症。我们有 先前确定并量化了NASH患者肝脏中发现的过量甘油三酯的来源 从血浆FFA池中，从膳食碳水化合物(CHO)和膳食脂肪中新合成的脂肪酸 在餐后进入肝脏。此外，我们还发现患病率存在显著的种族差异。 与高加索人和西班牙人相比，非洲裔美国人受到保护。临床 研究表明，减肥可以减少肝骨病，改善肝功能测试，并减少 NASH的肝纤维化。将进行临床试验，以比较两种不同的， 限制能量的饮食(低CHO和低脂肪)。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的非裔美国人)将随机选择两种饮食中的一种，以产生6%的 在5个月的时间内减肥。在减肥前后，我们将确定这些因素的相对效果 饮食对肝脏甘油三酯含量和炎症的影响 评估肝活检标本和临床化学。稳定的同位素，以及气相色谱/ 质谱学和核磁共振波谱将被用来表征和 比较两种饮食在不同种族人群中的代谢效果。这项研究是第一次 这两种方法同时用于评估体内代谢。这项研究是 旨在测试以下假设：H1，由于能量限制而导致的重量减轻，而不考虑 膳食中大量营养素的组成，会降低肝脏中甘油三酯的含量；与低脂饮食相比，H2为低CHO 饮食将显著减少炎症，与胰岛素敏感性的更大改善相一致； SMI配型的人在肝脏胰岛素抵抗、脂肪生成和/或膳食脂肪酸流量方面的差异 西班牙裔和非裔美国人将解释限制饮食CHO对降低肝脏脂肪的影响。通过 在NASH中更好地发现肝脏糖和脂代谢之间的相互关系 将了解引起NASH的代谢机制，目标是更有效 未来肥胖和糖尿病相关肝病的治疗策略。

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.