Iozzo Patricia, Guzzardi Maria Angela
Institute of Clinical Physiology, National Research Council (CNR), Pisa, Italy.
Endocr Connect. 2019 Nov;8(11):R169-R183. doi: 10.1530/EC-19-0348.
The prevalence of obesity has reached epidemic proportions and keeps growing. Obesity seems implicated in the pathogenesis of cognitive dysfunction, Alzheimer's disease and dementia, and vice versa. Growing scientific efforts are being devoted to the identification of central mechanisms underlying the frequent association between obesity and cognitive dysfunction. Glucose brain handling undergoes dynamic changes during the life-course, suggesting that its alterations might precede and contribute to degenerative changes or signaling abnormalities. Imaging of the glucose analog 18F-labeled fluorodeoxyglucose (18FDG) by positron emission tomography (PET) is the gold-standard for the assessment of cerebral glucose metabolism in vivo. This review summarizes the current literature addressing brain glucose uptake measured by PET imaging, and the effect of insulin on brain metabolism, trying to embrace a life-course vision in the identification of patterns that may explain (and contribute to) the frequent association between obesity and cognitive dysfunction. The current evidence supports that brain hypermetabolism and brain insulin resistance occur in selected high-risk conditions as a transient phenomenon, eventually evolving toward normal or low values during life or disease progression. Associative studies suggest that brain hypermetabolism predicts low BDNF levels, hepatic and whole body insulin resistance, food desire and an unfavorable balance between anticipated reward from food and cognitive inhibitory control. Emerging mechanistic links involve the microbiota and the metabolome, which correlate with brain metabolism and cognition, deserving attention as potential future prevention targets.
肥胖的患病率已达到流行程度且仍在不断上升。肥胖似乎与认知功能障碍、阿尔茨海默病和痴呆症的发病机制有关，反之亦然。越来越多的科研工作致力于确定肥胖与认知功能障碍频繁关联背后的中枢机制。葡萄糖在大脑中的处理在生命过程中会发生动态变化，这表明其改变可能先于退行性变化或信号异常并促成这些变化。通过正电子发射断层扫描（PET）对葡萄糖类似物18F标记的氟脱氧葡萄糖（18FDG）进行成像，是体内评估脑葡萄糖代谢的金标准。本综述总结了目前关于通过PET成像测量脑葡萄糖摄取以及胰岛素对脑代谢影响的文献，试图从生命过程的角度来识别可能解释（并促成）肥胖与认知功能障碍频繁关联的模式。目前的证据支持，在特定的高危情况下，脑代谢亢进和脑胰岛素抵抗作为一种短暂现象出现，最终在生命过程或疾病进展中朝着正常或低值发展。相关性研究表明，脑代谢亢进预示着脑源性神经营养因子（BDNF）水平较低、肝脏和全身胰岛素抵抗、食物欲望以及食物预期奖励与认知抑制控制之间的不利平衡。新出现的机制联系涉及微生物群和代谢组，它们与脑代谢和认知相关，作为潜在的未来预防靶点值得关注。
