Department of Neurology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
Psychoneuroendocrinology. 2019 Apr;102:128-138. doi: 10.1016/j.psyneuen.2018.12.003. Epub 2018 Dec 6.
Maternal environmental factors such as diet have profound effects on offspring development and later health. The hypothalamic-pituitary-adrenal (HPA) axis is an important stress neuroendocrine system that is subject to programming by early life challenges. The present study was further to investigate whether maternal high fat diet (HFD) exposure during rat pregnancy and lactation can alter the HPA axis activity in adult male offspring. We observed that maternal HFD consumption exerted long-term effects on the basal activity of the HPA axis in adult offspring, with increased mean plasma corticosterone levels that result from elevated steroid pulse frequence and pulse amplitude. More importantly, maternal HFD offspring displayed enhanced corticosterone responses to restraint (1 h) and lipopolysaccharide (25 μg/kg, iv) but not insulin-induced hypoglycemia (0.3U/kg, iv) stress, suggesting a stressor-specific effect of maternal diet on the hyperresponsiveness of the HPA axis to stress. Additionally, maternal HFD exposure markedly attenuated the habituation of HPA responses to repeated restraint stress. These findings demonstrate that perinatal HFD exposure has a potent and long-lasting influence on development of neuroendocrine regulatory mechanisms. Maternal HFD consumption significantly increased basal corticotropin-releasing factor (CRF) mRNA expression in the paraventricular nucleus; nevertheless, similar increments in CRF mRNA levels following restraint were observed between maternal HFD offspring and control rats. Furthermore, the medial and central nuclei of amygdala played a pivotal role in maternal HFD-induced sensitization of the HPA response to psychological and systemic stress, respectively, suggesting that different neural pathways may mediate maternal HFD-induced HPA hyperresponsivity to different types of stressors. Take together, the long-term effects of maternal HFD challenge on the central regulation of the HPA axis, therefore, expose the adult offspring to greater HPA function throughout lifespan, in stressor-specific and region-specific manner.
母体环境因素，如饮食，对后代的发育和后期健康有深远影响。下丘脑-垂体-肾上腺（HPA）轴是一个重要的应激神经内分泌系统，容易受到早期生活挑战的编程影响。本研究进一步探讨了母体妊娠和哺乳期高脂肪饮食（HFD）暴露是否会改变成年雄性后代的 HPA 轴活性。我们观察到，母体 HFD 消耗对成年后代 HPA 轴的基础活性产生了长期影响，导致皮质酮水平升高，这是由于类固醇脉冲频率和幅度增加所致。更重要的是，母体 HFD 后代对束缚（1 小时）和脂多糖（25μg/kg，iv）应激的皮质酮反应增强，但对胰岛素诱导的低血糖（0.3U/kg，iv）应激没有反应增强，这表明母体饮食对 HPA 轴对应激的高反应性具有应激特异性影响。此外，母体 HFD 暴露明显减弱了 HPA 对重复束缚应激反应的适应。这些发现表明，围产期 HFD 暴露对神经内分泌调节机制的发育具有强大而持久的影响。母体 HFD 暴露显著增加了室旁核中促肾上腺皮质释放因子（CRF）mRNA 的表达；然而，在母体 HFD 后代和对照大鼠之间，束缚后 CRF mRNA 水平也出现了类似的增加。此外，杏仁核的内侧核和中央核分别在母体 HFD 诱导的 HPA 对心理和全身应激反应的敏化中起关键作用，这表明不同的神经通路可能介导母体 HFD 诱导的 HPA 对不同类型应激源的高反应性。总之，母体 HFD 挑战对 HPA 轴中枢调节的长期影响，使成年后代在特定的应激源和特定的区域中，在整个生命过程中暴露于更大的 HPA 功能之下。
