Department of Pharmacology, School of Medical Sciences, UNSW, Sydney, NSW 2052, Australia.
Nutrients. 2021 Jan 15;13(1):240. doi: 10.3390/nu13010240.
The widespread consumption of 'western'-style diets along with sedentary lifestyles has led to a global epidemic of obesity. Epidemiological, clinical and preclinical evidence suggests that maternal obesity, overnutrition and unhealthy dietary patterns programs have lasting adverse effects on the physical and mental health of offspring. We review currently available preclinical and clinical evidence and summarise possible underlying neurobiological mechanisms by which maternal overnutrition may perturb offspring cognitive function, affective state and psychosocial behaviour, with a focus on (1) neuroinflammation; (2) disrupted neuronal circuities and connectivity; and (3) dysregulated brain hormones. We briefly summarise research implicating the gut microbiota in maternal obesity-induced changes to offspring behaviour. In animal models, maternal obesogenic diet consumption disrupts CNS homeostasis in offspring, which is critical for healthy neurodevelopment, by altering hypothalamic and hippocampal development and recruitment of glial cells, which subsequently dysregulates dopaminergic and serotonergic systems. The adverse effects of maternal obesogenic diets are also conferred through changes to hormones including leptin, insulin and oxytocin which interact with these brain regions and neuronal circuits. Furthermore, accumulating evidence suggests that the gut microbiome may directly and indirectly contribute to these maternal diet effects in both human and animal studies. As the specific pathways shaping abnormal behaviour in offspring in the context of maternal obesogenic diet exposure remain unknown, further investigations are needed to address this knowledge gap. Use of animal models permits investigation of changes in neuroinflammation, neurotransmitter activity and hormones across global brain network and sex differences, which could be directly and indirectly modulated by the gut microbiome.
随着“西式”饮食和久坐生活方式的广泛普及，肥胖已在全球流行。流行病学、临床和临床前证据表明，母体肥胖、营养过剩和不健康的饮食模式会对后代的身心健康产生持久的不良影响。我们回顾了目前可用的临床前和临床证据，并总结了母体营养过剩可能破坏后代认知功能、情绪状态和社会行为的潜在神经生物学机制，重点关注（1）神经炎症；（2）神经元回路和连接的中断；以及（3）大脑激素失调。我们简要总结了肠道微生物群在母体肥胖引起的后代行为变化中的研究。在动物模型中，母体肥胖饮食通过改变下丘脑和海马体的发育以及神经胶质细胞的募集，破坏了中枢神经系统的内稳态，这对健康的神经发育至关重要，随后还会使多巴胺能和 5-羟色胺能系统失调。母体肥胖饮食的不良影响还通过包括瘦素、胰岛素和催产素在内的激素变化传递，这些激素与这些大脑区域和神经元回路相互作用。此外，越来越多的证据表明，肠道微生物组可能直接和间接地促成了人类和动物研究中母体饮食的这些影响。由于在母体肥胖饮食暴露的情况下，塑造后代异常行为的具体途径尚不清楚，因此需要进一步的研究来填补这一知识空白。使用动物模型可以调查神经炎症、神经递质活性和激素在整个大脑网络和性别差异中的变化，这些变化可能直接或间接地受到肠道微生物组的调节。
