Martins Marina Galleazzo, Abizaid Alfonso
Department of Neuroscience, Carleton University, Ottawa, Ontario, Canada.
Compr Physiol. 2025 Jun;15(3):e70020. doi: 10.1002/cph4.70020.
The maternal nutritional and/or metabolic environment is crucial for future offspring health outcomes, and impairments during critical periods of development can alter the development of brain circuits that regulate energy balance, predisposing individuals to metabolic disorders throughout life. Epigenetic changes, changes in cell number and/or organ structure, and cellular metabolic differentiation could be some of the fetal adaptations leading to the development of metabolic disorders later in life. Here, we review animal models showing that the nutritional environment to which the offspring are exposed during their perinatal life can influence the development of the hypothalamic melanocortin system, promoting increased feeding and fat deposition. Following maternal undernutrition, the development of obesity in the offspring may be related to decreased POMC neuronal function since birth. Similarly, maternal diabetes and obesity also induce hypothalamic changes that result in an imbalance in AgRP/NPY and POMC expression during adulthood. Widespread impairments in brain development may also induce a global downregulation of the melanocortin system. Furthermore, animal models highlight that the time and type of exposure are key to the offspring outcomes, as are their sex and age. Possible sex-specific differences remain unclear, as most studies have evaluated only the male offspring, despite females having an increased risk of developing obesity and gestational diabetes during their pregnancy, which imposes a transgenerational effect of metabolic disorders. Studies aiming at evaluating the long-term effects of the maternal nutritional environment in both males and females could help delineate how the susceptibility to metabolic disorders development worsens over time.
母体的营养和/或代谢环境对后代未来的健康状况至关重要，发育关键期的损害会改变调节能量平衡的脑回路发育，使个体终生易患代谢紊乱。表观遗传变化、细胞数量和/或器官结构的改变以及细胞代谢分化可能是导致个体日后发生代谢紊乱的一些胎儿适应性变化。在此，我们综述了动物模型，这些模型表明后代在围产期所接触的营养环境会影响下丘脑黑皮质素系统的发育，促进进食增加和脂肪沉积。母体营养不足后，后代肥胖的发生可能与出生后促黑素细胞激素（POMC）神经元功能下降有关。同样，母体糖尿病和肥胖也会诱发下丘脑变化，导致成年期刺鼠相关蛋白（AgRP）/神经肽Y（NPY）和POMC表达失衡。脑发育的广泛损害也可能导致黑皮质素系统整体下调。此外，动物模型强调暴露的时间和类型对后代结局至关重要，其性别和年龄也是如此。可能存在的性别差异仍不明确，因为大多数研究仅评估了雄性后代，尽管女性在孕期患肥胖症和妊娠糖尿病的风险增加，这会产生代谢紊乱的跨代效应。旨在评估母体营养环境对雄性和雌性长期影响的研究有助于阐明代谢紊乱易感性如何随时间恶化。
