Hypothalamic Fatty Acid Sensing in Aging

衰老中的下丘脑脂肪酸感应

基本信息

批准号：
7569480
负责人：
Rachel A Ross
金额：
$ 4.62万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-02-15 至 2010-03-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7569480
关键词：
Acids Address Age Aging Albumins Animal Model Animals Biochemical Blood Circulation Brain Caloric Restriction Carnitine Carnitine O-Palmitoyltransferase Catalytic RNA Cell Nucleus Cell physiology Cells Cellular Membrane Chylomicrons Coenzyme A Data Defect Dependovirus Development Down-Regulation Enzymes Equilibrium Esterification Fatty Acids Glucose Goals Hormones Hydrolysis Hypothalamic structure Insulin Insulin Resistance Intake Lead Learning Length Leptin Life Style Lipids Lipoproteins Liver Longevity Malonyl Coenzyme A Medical Metabolic Metabolic syndrome Metabolism Mitochondria Molecular Monounsaturated Fatty Acids Neuraxis Nutrient Obesity Pathway interactions Peripheral Physiological Play Process Production Protein Isoforms Rattus Regulation Role Scientist Signal Transduction Source Techniques Testing Transferase Triglycerides base blood glucose regulation detection of nutrient fatty acid metabolism fatty acid oxidation glucose metabolism improved insulin sensitivity long chain fatty acid malonyl-CoA decarboxylase oxidation research study response restoration sedentary sensor uptake

项目摘要

DESCRIPTION (provided by applicant): The goal of this thesis project is to determine whether the metabolism of fatty acid within the hypothalamus plays an important role in the regulation of energy and glucose homeostasis in aging. Specifically, I plan to induce bi-directional changes in the hypothalamic expression of two critical enzymes in fatty acid metabolism: malonyl-CoA decarboxylase (MOD) and carnitine palmitoyl transferase 1 (CPT1) and then examine their impact on the metabolic syndrome of aging in rats. I will pursue two experimental aims. 1) Identify the role of malonyl-CoA in the development of the metabolic syndrome of aging. I postulate that decreased cellular levels of malonyl-CoA lead to the progressive loss of lipid (and other nutrient) sensing in the hypothalamus of aging rats 2) Identify the role of LCFA-CoA in the development of the metabolic syndrome of aging. I postulate that decreased cellular levels of LCFA-CoA lead to the progressive loss of lipid (and other nutrient) sensing in the hypothalamus of aging rats. In doing these experiments, I will learn multiple physiologic, pharmacologic, and molecular techniques that will help me grow into an independent scientist while solving an important medical problem.

描述（由申请人提供）：本论文项目的目标是确定下丘脑内的脂肪酸代谢是否在衰老过程中能量和葡萄糖稳态的调节中发挥重要作用。具体来说，我计划诱导脂肪酸代谢中两种关键酶的下丘脑表达的双向变化：丙二酰辅酶A脱羧酶（MOD）和肉碱棕榈酰转移酶1（CPT1），然后检查它们对衰老代谢综合征的影响老鼠。我将追求两个实验目标。 1) 确定丙二酰辅酶A在衰老代谢综合征发展中的作用。我推测丙二酰辅酶 A 的细胞水平降低会导致衰老大鼠下丘脑中脂质（和其他营养物质）感知的逐渐丧失。 2) 确定 LCFA-CoA 在衰老代谢综合征发展中的作用。我推测细胞中 LCFA-CoA 水平的降低会导致衰老大鼠下丘脑中脂质（和其他营养物质）感知能力逐渐丧失。在进行这些实验时，我将学习多种生理学、药理学和分子技术，这些技术将帮助我成长为一名独立的科学家，同时解决重要的医学问题。