Reynolds Clare M, Segovia Stephanie A, Vickers Mark H
Liggins Institute, University of Auckland, Auckland, New Zealand.
Front Endocrinol (Lausanne). 2017 Sep 25;8:245. doi: 10.3389/fendo.2017.00245. eCollection 2017.
Evidence from epidemiological, clinical, and experimental studies have clearly shown that disease risk in later life is increased following a poor early life environment, a process preferentially termed developmental programming. In particular, this work clearly highlights the importance of the nutritional environment during early development with alterations in maternal nutrition, including both under- and overnutrition, increasing the risk for a range of cardiometabolic and neurobehavioral disorders in adult offspring characterized by both adipokine resistance and obesity. Although the mechanistic basis for such developmental programming is not yet fully defined, a common feature derived from experimental animal models is that of alterations in the wiring of the neuroendocrine pathways that control energy balance and appetite regulation during early stages of developmental plasticity. The adipokine leptin has also received significant attention with clear experimental evidence that normal regulation of leptin levels during the early life period is critical for the normal development of tissues and related signaling pathways that are involved in metabolic and cardiovascular homeostasis. There is also increasing evidence that alterations in the epigenome and other underlying mechanisms including an altered gut-brain axis may contribute to lasting cardiometabolic dysfunction in offspring. Ongoing studies that further define the mechanisms between these associations will allow for identification of early risk markers and implementation of strategies around interventions that will have obvious beneficial implications in breaking a programmed transgenerational cycle of metabolic disorders.
流行病学、临床及实验研究的证据已清楚表明，早年生活环境不佳会增加晚年患病风险，这一过程被优先称为发育编程。特别是，这项工作清楚地凸显了早期发育期间营养环境的重要性，母体营养的改变，包括营养不足和营养过剩，都会增加成年后代患一系列以脂肪因子抵抗和肥胖为特征的心脑血管及神经行为障碍的风险。尽管这种发育编程的机制基础尚未完全明确，但实验动物模型的一个共同特征是，在发育可塑性早期阶段，控制能量平衡和食欲调节的神经内分泌通路的连接发生了改变。脂肪因子瘦素也受到了极大关注，有明确的实验证据表明，早年时期瘦素水平的正常调节对于参与代谢和心血管稳态的组织及相关信号通路的正常发育至关重要。越来越多的证据表明，表观基因组的改变以及包括肠道-脑轴改变在内的其他潜在机制，可能导致后代持续的心脑血管功能障碍。进一步明确这些关联之间机制的正在进行的研究，将有助于识别早期风险标志物，并实施围绕干预措施的策略，这对于打破代谢紊乱的程序化跨代循环将具有明显的有益影响。
