Substrate Cycling in Energy Metabolism

能量代谢中的底物循环

• 批准号: 8068084
• 负责人: ROBERT R WOLFE
• 金额: $ 9.34万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-18 至 2010-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8068084
• 关键词: Adipose tissue; Albumins; Animal Model; Apolipoproteins B; Burn injury; C-reactive protein; Cells; Coupled; Development; Diet; Dietary Proteins; Energy Intake; Energy Metabolism; Family suidae; Fatty Acids; Grant; Hepatic; Human; Hypertriglyceridemia; Immune; Inflammatory; Ingestion; Insulin Resistance; Intake; Intracellular Accumulation of Lipids; Lipids; Liver; Maintenance; Metabolic; Muscle; Nutritional Support; Palmitoyl Coenzyme A; Patients; Peripheral; Plasma; Production; Proteins; Site; Substrate Cycling; Time; Tracer; Triglycerides; Very low density lipoprotein; Wound Healing; cytokine; direct application; glucose production; immune function; improved; indexing; injured; instrument; insulin sensitivity; lipoprotein lipase; public health relevance; stable isotope; trafficking; very low density lipoprotein triglyceride; wound

DESCRIPTION (provided by applicant): We have previously shown that accumulation of both peripheral and hepatic intracellular triglycerides (TGs) occurs following severe burn injury in both human patients and in a porcine animal model. This accumulation of intracellular lipids is associated in time with the development of insulin resistance both at the liver and in the muscle. Our overriding hypothesis is that accumulation of hepatic TG and related lipids induce hepatic insulin resistance following burn injury. We will use the animal model to further examine the mechanisms responsible for hepatic TG accumulation and the relation of increased hepatic TGs to insulin sensitivity. We will investigate the three aspects of hepatic TG accumulation- TG production, secretion as VLDL, and peripheral VLDL clearance. In particular, we will focus on dietary approaches to stimulating VLDL secretion and clearance and reducing hepatic TG production. Our hypothesis is that a hypocaloric diet coupled with an increased protein intake will decrease hepatic storage of TGs, and thereby improve insulin sensitivity. We propose that this is an interactive effect, meaning that neither the hypocaloric diet nor high protein alone will have the same effect as the combination of the two. We further propose that improved insulin sensitivity will be reflected in improved wound healing, maintenance of lean mass and immune function. Studies will be performed in chronically instrumented pigs using stable isotope tracer approaches to quantify appropriate metabolic parameters. The results from these studies will have direct application in the nutritional care of severely burned or injured patients. PUBLIC HEALTH RELEVANCE: Our overriding hypothesis is that accumulation of hepatic TG and related lipids induce hepatic insulin resistance following burn injury. Our central hypothesis is that a hypocaloric diet coupled with an increased protein intake will decrease hepatic storage of TGs, and thereby improve insulin sensitivity. We further propose that improved insulin sensitivity will be reflected in improved wound healing, maintenance of lean mass and immune function. The results from these studies will have direct application in the nutritional care of severely burned or injured patients.

描述（由申请人提供）：我们之前已经表明，在人类患者和猪动物模型中，严重烧伤后会发生外周和肝细胞内甘油三酯（TG）的积累。细胞内脂质的积累与肝脏和肌肉中胰岛素抵抗的发展有关。我们最重要的假设是，烧伤后肝脏 TG 和相关脂质的积累会诱导肝脏胰岛素抵抗。我们将利用动物模型进一步研究肝脏TG积累的机制以及肝脏TG增加与胰岛素敏感性的关系。我们将研究肝脏 TG 积累的三个方面——TG 产生、VLDL 分泌和外周 VLDL 清除。特别是，我们将重点关注刺激 VLDL 分泌和清除以及减少肝脏 TG 产生的饮食方法。我们的假设是，低热量饮食加上增加蛋白质摄入量将减少肝脏对甘油三酯的储存，从而提高胰岛素敏感性。我们认为这是一种交互作用，这意味着单独的低热量饮食和高蛋白饮食都不会与两者的组合产生相同的效果。我们进一步提出，胰岛素敏感性的提高将体现在伤口愈合的改善、瘦体重的维持和免疫功能上。研究将在长期使用仪器的猪中进行，使用稳定同位素示踪剂方法来量化适当的代谢参数。这些研究的结果将直接应用于严重烧伤或受伤患者的营养护理。 公共健康相关性：我们最重要的假设是，烧伤后肝脏 TG 和相关脂质的积累会诱发肝脏胰岛素抵抗。我们的中心假设是，低热量饮食加上增加蛋白质摄入量将减少肝脏对甘油三酯的储存，从而提高胰岛素敏感性。我们进一步提出，胰岛素敏感性的提高将体现在伤口愈合的改善、瘦体重的维持和免疫功能上。这些研究的结果将直接应用于严重烧伤或受伤患者的营养护理。