Sanguinetti Elena, Liistro Tiziana, Mainardi Marco, Pardini Silvia, Salvadori Piero A, Vannucci Alessandro, Burchielli Silvia, Iozzo Patricia
Institute of Clinical Physiology, National Research Council (CNR), via Moruzzi 1, Pisa, 56124, Italy.
Scuola Superiore di Studi Universitari Sant'Anna, Pisa, Italy.
Diabetologia. 2016 Apr;59(4):813-21. doi: 10.1007/s00125-015-3848-5. Epub 2016 Jan 5.
AIMS/HYPOTHESIS: Maternal obesity negatively affects fetal development. Abnormalities in brain glucose metabolism are predictive of metabolic-cognitive disorders.
We studied the offspring (aged 0, 1, 6, 12 months) of minipigs fed a normal vs high-fat diet (HFD), by positron emission tomography (PET) to measure brain glucose metabolism, and ex vivo assessments of brain insulin receptors (IRβ) and GLUT4.
At birth, brain glucose metabolism and IRβ were twice as high in the offspring of HFD-fed than control mothers. During infancy and youth, brain glucose uptake, GLUT4 and IRβ increased in the offspring of control mothers and decreased in those of HFD-fed mothers, leading to a 40-85% difference (p < 0.05), and severe glycogen depletion, lasting until adulthood.
CONCLUSIONS/INTERPRETATION: Maternal high-fat feeding leads to brain glucose overexposure during fetal development, followed by long-lasting depression in brain glucose metabolism in minipigs. These features may predispose the offspring to develop metabolic-neurodegenerative diseases.
目的/假设：母亲肥胖会对胎儿发育产生负面影响。脑葡萄糖代谢异常可预测代谢性认知障碍。
我们通过正电子发射断层扫描（PET）测量脑葡萄糖代谢，并对脑胰岛素受体（IRβ）和葡萄糖转运蛋白4（GLUT4）进行离体评估，研究了喂食正常饮食与高脂饮食（HFD）的小型猪的后代（0、1、6、12个月龄）。
出生时，喂食HFD的母亲的后代的脑葡萄糖代谢和IRβ是对照组母亲后代的两倍。在婴儿期和青年期，对照组母亲的后代的脑葡萄糖摄取、GLUT4和IRβ增加，而喂食HFD的母亲的后代则减少，导致差异达40 - 85%（p < 0.05），且严重糖原耗竭持续至成年期。
结论/解读：母亲高脂喂养导致胎儿发育期间脑葡萄糖过度暴露，随后小型猪脑葡萄糖代谢长期受抑制。这些特征可能使后代易患代谢性神经退行性疾病。
