The impact of obesity on cerebral glucose transport and metabolism

肥胖对脑葡萄糖转运和代谢的影响

基本信息

批准号：
10337054
负责人：
Janice Jin Hwang
金额：
$ 51.81万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-02-07 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10337054
关键词：
Acute Adult Age Alzheimer&apos s Disease Animal Model Automobile Driving Blood Blood - brain barrier anatomy Body mass index Brain Calories Cerebrum Clinical Closure by clamp Control Groups Coupled Cues Development Eating Failure Fat emulsion Fatty Acids Female Food Foundations Future Glucose Glucose Transporter Glycolysis Glycosylated hemoglobin A Goals High Fat Diet Hour Human Hyperglycemia Individual Infusion procedures Insulin Resistance Kinetics Lead Literature Magnetic Resonance Spectroscopy Maps Measurement Measures Mediating Metabolism Methodology Modeling Molecular Muscle Neuraxis Neurocognitive Neurodegenerative Disorders Nonesterified Fatty Acids Obesity Overweight Palmitic Acids Participant Pathogenesis Peripheral Persons Physiological Plasma Play Process Randomized Rattus Regulation Research Design Rodent Rodent Model Role SLC2A1 gene Saline Satiation Scanning Signal Pathway Signal Transduction Sweden Techniques Technology Thinness Tissues Visual cognitive function combat experimental study fatty acid oxidation frontal lobe glucose metabolism glucose transport glucose uptake male metabolic phenotype neuroimaging obese person oxidation prevent randomized controlled study regional difference response treatment strategy

项目摘要

Project summary There is a growing body of evidence that obesity is associated with reduced cerebral metabolism; however, the underlying mechanisms and the functional clinical implications of these observations remain unclear. The central goal of this project is to investigate a finding we have recently made that obesity is associated with decreased transport capacity for glucose across the blood-brain barrier. Furthermore, this association may be mediated by circulating fatty acids. This proposal uses state of the art neuroimaging technology coupled with classic human metabolic phenotyping methodologies to investigate the underlying mechanisms behind how the brain is impacted by obesity. Aim 1 of this project will determine whether obesity is associated with changes in brain glucose transport and metabolism using 13C magnetic resonance spectroscopy scanning. Aim 2 of this project will use a randomized controlled study design to assess whether acute elevations of circulating fatty acid levels amongst lean, healthy control subjects will lead to decreased brain glucose levels. Finally, Aim 3 of this project will use parallel studies using a rat model to investigate the underlying cellular mechanisms. Because the brain is exquisitely sensitive to circulating glucose levels, the findings from this proposed study will help clarify how diminished brain glucose transport in obesity may lead to diminished post-prandial satiety signaling and/or be a potential mechanism for the neurocognitive consequences of obesity.

项目概要越来越多的证据表明肥胖与脑代谢降低有关。然而，这些观察结果的潜在机制和功能性临床意义仍不清楚。这该项目的中心目标是调查我们最近的一项发现，即肥胖与葡萄糖穿过血脑屏障的运输能力降低。此外，该协会可能是由循环脂肪酸介导。该提案使用最先进的神经影像技术以及经典的人类代谢表型分析方法来研究背后的潜在机制大脑受到肥胖的影响。该项目的目标 1 将确定肥胖是否与使用 13C 磁共振波谱扫描进行大脑葡萄糖转运和代谢。这个目标2 项目将使用随机对照研究设计来评估循环脂肪是否急性升高瘦、健康对照受试者的酸水平会导致脑葡萄糖水平降低。最后，目标 3 该项目将使用大鼠模型进行平行研究来研究潜在的细胞机制。由于大脑对循环葡萄糖水平非常敏感，这项拟议研究的结果将有助于阐明肥胖引起的大脑葡萄糖转运减少如何导致餐后饱腹感减少信号传导和/或成为肥胖神经认知后果的潜在机制。