在美国，儿童低级别胶质瘤的发病率一直在上升，反映出儿童和孕产妇肥胖率的上升。最近，肥胖母亲的孩子被证明患脑瘤的几率更高。重要的是，鉴于高脂肪和高糖 (HFHS) 食物选择的普遍存在，美国的肥胖很大程度上是由饮食驱动的。由于高脂肪饮食暴露可以增加胚胎神经胶质祖细胞（NPC）的增殖，这是低级别神经胶质瘤的潜在细胞来源，因此我们假设在子宫内暴露于致肥胖饮食会通过影响肿瘤细胞来改变儿童大脑外显率和潜伏期我们采用了几种 1 型神经纤维瘤病 (NF1) 小儿脑肿瘤易感综合征的小鼠模型，其中视神经胶质瘤 (Nf1-OPG) 起源于胚胎第三脑室区 (TVZ) 的 NPC。我们将母鼠和后代暴露于导致肥胖的 HFHS 饮食或对照饲料中，并分析了 E19.5 时的胎儿神经发育和 6w-3mo 时的肿瘤形成。来自 HFHS 饮食的母鼠的后代表现出 TVZ NPC 增殖和神经胶质分化增加。饮食转换队列证实，这些影响取决于母亲的饮食，而不是母亲的体重。致肥饮食（Ob）同样加速了高外显率 Nf1-OPG 菌株中的神经胶质瘤形成，并增加了两种低外显率 Nf1-OPG 菌株中的神经胶质瘤外显率。相比之下，仅在产后接触 Ob 并不能重现这些影响。这些发现表明，母亲肥胖饮食是小鼠 Nf1-OPG 形成的危险因素，部分通过子宫内对肿瘤细胞来源的影响发挥作用。© 作者(s) 2024。由牛津大学出版社代表神经肿瘤学会出版。版权所有。如需商业重复使用，请联系 reprints@oup.com 获取转载和转载的翻译权。所有其他权限都可以通过我们网站文章页面上的权限链接通过我们的 RightsLink 服务获得 - 如需了解更多信息，请联系journals.permissions@oup.com。

Pediatric low-grade glioma incidence has been rising in the U.S., mirroring the rising rates of pediatric and maternal obesity. Recently, children of obese mothers were demonstrated to develop brain tumors at higher rates. Importantly, obesity in the U.S. is largely driven by diet, given the prevalence of high fat and high sugar (HFHS) food choices. Since high-fat diet exposure can increase embryonic neuroglial progenitor cell (NPC) proliferation, the potential cells of origin for low-grade glioma, we hypothesized that in utero exposure to an obesogenic diet would modify pediatric brain penetrance and latency by affecting the tumor cell of origin.We employed several murine models of the Neurofibromatosis type 1 (NF1) pediatric brain tumor predisposition syndrome, in which optic pathway gliomas (Nf1-OPGs) arise from NPCs in the embryonic third ventricular zone (TVZ). We exposed dams and offspring to an obesogenic HFHS diet or control chow and analysed fetal neurodevelopment at E19.5 and tumor formation at 6w-3mo.Progeny from HFHS diet-exposed dams demonstrated increased TVZ NPC proliferation and glial differentiation. Dietary switch cohorts confirmed that these effects were dependent upon maternal diet, rather than maternal weight. Obesogenic diet (Ob) similarly accelerated glioma formation in a high-penetrance Nf1-OPG strain and increased glioma penetrance in two low-penetrance Nf1-OPG strains. In contrast, Ob exposure in the postnatal period alone did not recapitulate these effects.These findings establish maternal obesogenic diet as a risk factor for murine Nf1-OPG formation, acting in part through in utero effects on the tumor cell of origin.© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.