Urbonaite Gintare, Knyzeliene Agne, Bunn Fanny Sophia, Smalskys Adomas, Neniskyte Urte
Institute of Biosciences, Life Sciences Center, Vilnius University, Vilnius, Lithuania.
Centre for Cardiovascular Science, The Queen's Medical Research Centre, The University of Edinburgh, Edinburgh, United Kingdom.
Front Neurosci. 2022 Jul 22;16:909762. doi: 10.3389/fnins.2022.909762. eCollection 2022.
A maternal high-fat diet affects offspring neurodevelopment with long-term consequences on their brain health and behavior. During the past three decades, obesity has rapidly increased in the whole human population worldwide, including women of reproductive age. It is known that maternal obesity caused by a high-fat diet may lead to neurodevelopmental disorders in their offspring, such as autism spectrum disorder, attention deficit hyperactivity disorder, anxiety, depression, and schizophrenia. A maternal high-fat diet can affect offspring neurodevelopment due to inflammatory activation of the maternal gut, adipose tissue, and placenta, mirrored by increased levels of pro-inflammatory cytokines in both maternal and fetal circulation. Furthermore, a maternal high fat diet causes gut microbial dysbiosis further contributing to increased inflammatory milieu during pregnancy and lactation, thus disturbing both prenatal and postnatal neurodevelopment of the offspring. In addition, global molecular and cellular changes in the offspring's brain may occur due to epigenetic modifications including the downregulation of brain-derived neurotrophic factor (BDNF) expression and the activation of the endocannabinoid system. These neurodevelopmental aberrations are reflected in behavioral deficits observed in animals, corresponding to behavioral phenotypes of certain neurodevelopmental disorders in humans. Here we reviewed recent findings from rodent models and from human studies to reveal potential mechanisms by which a maternal high-fat diet interferes with the neurodevelopment of the offspring.
母亲的高脂饮食会影响后代的神经发育，对其大脑健康和行为产生长期影响。在过去三十年中，全球整个人口中肥胖率迅速上升，包括育龄妇女。众所周知，高脂饮食导致的母亲肥胖可能会导致其后代出现神经发育障碍，如自闭症谱系障碍、注意力缺陷多动障碍、焦虑症、抑郁症和精神分裂症。母亲的高脂饮食会因母亲肠道、脂肪组织和胎盘的炎症激活而影响后代的神经发育，母婴循环中促炎细胞因子水平的升高反映了这一点。此外，母亲的高脂饮食会导致肠道微生物失调，进一步加剧孕期和哺乳期的炎症环境，从而干扰后代的产前和产后神经发育。此外，由于表观遗传修饰，包括脑源性神经营养因子（BDNF）表达下调和内源性大麻素系统激活，后代大脑可能会发生整体分子和细胞变化。这些神经发育异常反映在动物身上观察到的行为缺陷中，与人类某些神经发育障碍的行为表型相对应。在此，我们综述了来自啮齿动物模型和人类研究的最新发现，以揭示母亲高脂饮食干扰后代神经发育的潜在机制。
