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Triglyceride Rich Lipoprotein Metabolism and Fatty Acid Selectivity

富含甘油三酯的脂蛋白代谢和脂肪酸选择性

基本信息

批准号：
8325590
负责人：
ROBERT Henry NELSON
金额：
$ 14.32万
依托单位：
MAYO CLINIC ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-30 至 2013-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8325590
关键词：
Abdomen Address Adipocytes Adipose tissue Appearance Behavior Blood Pressure Chylomicrons Communities Development Diabetes Mellitus Diet Dilution Techniques Emulsions Enteral Epidemiology Epinephrine Etiology Fatty Acids Functional disorder Glucose Goals High Pressure Liquid Chromatography Hormones Human Infusion procedures Ingestion Insulin Intravenous infusion procedures Investigation Knowledge Label Lipids Lipolysis Lipoproteins Measurement Measures Metabolic Metabolism Muscle Non-Insulin-Dependent Diabetes Mellitus Nonesterified Fatty Acids Oral Palmitates Pancreas Pharmacologic Substance Plasma Plethysmography Polyunsaturated Fatty Acids Prevention Process Research Personnel Saline Saturated Fatty Acids Structure Testing Tracer Triglycerides Tumor Necrosis Factor-alpha Unsaturated Fatty Acids adiponectin base extracellular fatty acid metabolism inflammatory marker insulin sensitivity lipid metabolism lipoprotein lipase liquid chromatography mass spectroscopy obesity treatment research study skills subcutaneous uptake

项目摘要

DESCRIPTION (provided by applicant): Understanding the details of metabolism of lipids in normal humans is essential to the development of effective dietary and pharmaceutical prevention and treatment of obesity and type 2 diabetes. The fundamental processes of fatty acid release from adipocytes, the uptake of plasma free fatty acids by muscle and adipose tissue and the contribution of extracellular lipolysis of triglyceride rich lipoproteins to the free fatty acid pool are only partially understood. Epidemiologic and dietary studies suggest that there are differences in fatty acid metabolism based on fatty acid structure (saturated, monounsaturated or polyunsaturated). This proposal addresses gaps in the knowledge of fatty acid metabolism by testing the following hypotheses: 1. Oleate and palmitate generated by lipoprotein lipase lipolysis of circulating triglycerides spill over into the plasma free fatty acid pool more than linoleate. 2. Adipose tissue releases fatty acids selectively. 3. Changes in insulin sensitivity, endothelial function and blood pressure vary by the structure of fatty acids infused enterally to elevate free fatty acids. These hypotheses will be tested using triglyceride and fatty acid tracer dilution techniques, high performance liquid chromatography and mass spectroscopy. Two of the studies will be done using intravenous infusion tracers with one study also using oral lipid tracers. Specific aim 1 uses tracers with a mixed meal, specific aim 2 utilizes tracers with hormone infusions and specific aim 3 uses oral unlabeled fatty acid infusion in the form of a triglyceride with a pure fatty acid structure with measures of endothelial dysfunction, blood pressure, insulin sensitivity and changes in inflammatory markers compared to saline ingestion. These studies will provide the applicant with an opportunity to develop further the skills necessary to achieve his long-term goal of becoming an independent investigator exploring the relationship between lipid metabolism and diabetes.

描述（由申请人提供）：了解正常人脂质代谢的细节对于开发有效的饮食和药物预防和治疗肥胖和2型糖尿病至关重要。从脂肪细胞释放脂肪酸的基本过程，肌肉和脂肪组织对血浆游离脂肪酸的摄取，以及富含甘油三酯的脂蛋白的细胞外脂解对游离脂肪酸池的贡献仅部分了解。流行病学和饮食研究表明，基于脂肪酸结构（饱和、单不饱和或多不饱和）的脂肪酸代谢存在差异。本提案通过检验以下假设，填补了脂肪酸代谢知识方面的空白： 1.循环甘油三酯的脂蛋白脂肪酶脂解产生的油酸和棕榈酸比亚油酸更多地溢出到血浆游离脂肪酸池中。 2.脂肪组织选择性地释放脂肪酸。 3.胰岛素敏感性、内皮功能和血压的变化因肠内输注脂肪酸以提高游离脂肪酸的结构而异。将使用甘油三酯和脂肪酸示踪稀释技术、高效液相色谱法和质谱法对这些假设进行检验。其中两项研究将使用静脉输注示踪剂进行，一项研究还使用口服脂质示踪剂。具体目标1使用示踪剂与混合膳食，具体目标2使用示踪剂与激素输注，具体目标3使用具有纯脂肪酸结构的甘油三酯形式的口服未标记脂肪酸输注，与盐水摄入相比，测量内皮功能障碍、血压、胰岛素敏感性和炎症标志物的变化。这些研究将为申请人提供进一步发展必要技能的机会，以实现其长期目标，即成为探索脂质代谢和糖尿病之间关系的独立研究者。