Fatty Acid Oxidation Disorders & Body Weight Regulation

脂肪酸氧化障碍

• 批准号: 7095741
• 负责人: Melanie B Gillingham
• 金额: $ 10.18万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7095741
• 关键词: adolescence (12-20); bioenergetics; body composition; body weight; caloric dietary content; clinical research; diet therapy; dietary lipid; dietary proteins; fatty acid metabolism; fatty acids; ghrelin; glucose tolerance; human subject; human therapy evaluation; inborn metabolism disorder; insulin; leptin; lipid biosynthesis; middle childhood (6-11); neuroendocrine system; obesity; patient oriented research

DESCRIPTION (provided by applicant): This application proposes a training program to transition Melanie B. Gillingham, PhD from a post-doctoral to a faculty position and independent clinical investigator. Dr. Gillingham is completing her fourth year of post-doctoral training in Medical and Molecular Genetics at OHSU. She has accepted an position as an assistant professor in the graduate Clinical Nutrition program, Division of Endocrinology, Diabetes and Clinical Nutrition. The primary goal of this program will be for Dr. Gillingham to achieve independence as a clinical investigator in all respects. The mentored career development plan consists of a two-tiered approach: a focused didactic and experitential learning program in a new area of interest and a mentored clinical research experiance. The learning program will consist of didactic training in neuroendocrine body weight regulation and stable isotope techniques and learning a new laboratory method, isotope ratio mass spectroscopy (IRMS) under the direction of Dr. Dale Schoeller at the University of Wisconsin-Madison. The mentored research will be conduced under the direction of Jonathan Purnell, MD and Cary O. Harding, MD. The goal of the research is to investigate the effects of fatty acid oxidation (FAO) on body composition and weight regulation using the following long-chain FAO disorders as models: inherited deficiency of trifunctional protein and very long-chain acyl-CoA dehydrogenase. Fatty acid beta-oxidation is an important regulatory element in the regulation of food intake and body weight, as well as in the expression of insulin resistance and dyslipidemia. Children with long-chain FAO disorders lack an ability to oxidize fatty acids for energy. They have elevated de novo lipogenesis, and increased body fat. Ectopic fat deposition in the liver and muscle is closely associated with insulin resistance and cardiovascular disease, but the relationship between fatty acid oxidation, energy balance and ectopic fat deposition is not fully understood. We propose to study the regulation of body composition and macronutrient metabolism in children with long-chain FAO disorders compared to normal controls. We also propose to determine the effects of an increased protein, low fat diet on body composition in children with long-chain FAO disorders. Results from these studies will enhance our understanding of the role of FAO in body composition and insulin resistance, and may provide a new dietary treatment to prevent obesity in children with long-chain FAO disorders.

描述（由申请人提供）： 本申请提出了一个培训计划，以过渡梅兰妮B。吉灵厄姆，博士从博士后到教师职位和独立的临床研究者。吉灵厄姆博士正在完成她在OHSU的医学和分子遗传学博士后培训的第四年。她已经接受了一个职位，作为一个助理教授在研究生临床营养计划，内分泌学，糖尿病和临床营养部。该计划的主要目标是让吉灵厄姆博士在各方面实现作为临床研究者的独立性。指导的职业发展计划包括两个层次的方法：在一个新的感兴趣的领域和指导的临床研究经验的重点教学和体验式学习计划。该学习计划将包括神经内分泌体重调节和稳定同位素技术的教学培训，以及在威斯康星大学麦迪逊分校Dale Schoeller博士的指导下学习新的实验室方法--同位素比质谱法（IRMS）。指导研究将在Jonathan Purnell，MD和卡里O的指导下进行。Harding，MD.本研究的目的是研究脂肪酸氧化（FAO）对身体组成和体重调节的影响，使用以下长链FAO疾病作为模型：遗传性三功能蛋白质缺乏症和极长链酰基辅酶A脱氢酶。脂肪酸β-氧化是调节食物摄入和体重的重要调节元件，也是胰岛素抵抗和血脂异常的表达中的重要调节元件。患有长链FAO疾病的儿童缺乏氧化脂肪酸获取能量的能力。他们有升高的从头脂肪生成，并增加身体脂肪。肝脏和肌肉中的异位脂肪沉积与胰岛素抵抗和心血管疾病密切相关，但脂肪酸氧化，能量平衡和异位脂肪沉积之间的关系尚未完全了解。我们建议研究与正常对照组相比，长链FAO疾病的儿童的身体组成和宏量营养素代谢的调节。我们还建议确定增加蛋白质，低脂肪饮食对长链FAO疾病儿童身体组成的影响。这些研究的结果将增强我们对FAO在身体组成和胰岛素抵抗中的作用的理解，并可能提供一种新的饮食治疗方法，以预防患有长链FAO疾病的儿童肥胖。