The impact of obesity on cerebral glucose transport and metabolism

项目总结 越来越多的证据表明，肥胖与大脑新陈代谢降低有关；然而， 这些观察结果的潜在机制和功能临床意义尚不清楚。这个 这个项目的中心目标是调查我们最近发现的肥胖与 降低了葡萄糖通过血脑屏障的运输能力。此外，这种关联可能是 由循环中的脂肪酸调节。这项提议使用了最先进的神经成像技术， 经典的人类代谢表型方法，以研究其背后的潜在机制 大脑受到肥胖的影响。该项目的目标1将确定肥胖是否与 用~(13)C磁共振波谱扫描研究脑内葡萄糖的转运和代谢。目标2 该项目将使用随机对照研究设计来评估循环脂肪的急性升高 健康瘦身的受试者体内的酸度会导致大脑葡萄糖水平降低。最后，目标3 该项目将使用大鼠模型进行平行研究，以研究潜在的细胞机制。 由于大脑对循环中的血糖水平非常敏感，这项拟议的研究结果 将有助于阐明肥胖患者大脑葡萄糖转运减少如何导致餐后饱腹感减弱 信号和/或是肥胖的神经认知后果的潜在机制。

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.