Elsakr Joseph M, Gannon Maureen
Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA.
Department of Veterans Affairs, Tennessee Valley Health Authority, Vanderbilt University, Nashville, TN 37232, USA.
Trends Dev Biol. 2017;10:79-95.
The Developmental Origins of Health and Disease (DOHaD) Hypothesis postulates that the environment influences postnatal health and plays a role in disease etiology. Studies in both humans and animal models have shown that exposure to either under- or overnutrition results in an increased risk of metabolic disease later in life. In addition, offspring born to overweight or obese mothers are more likely to be obese as children and into early adulthood and to have impaired glucose tolerance as adults. The Centers for Disease Control and Prevention estimates that over 70% of adults over the age of 20 are either overweight or obese and that nearly half of women are either overweight or obese at the time they become pregnant. Thus, the consequences of maternal overnutrition on the developing fetus are likely to be realized in greater numbers in the coming decades. This review will focus specifically on the effects of overnutrition on pancreatic islet development and function and how the resulting morphological and functional changes influence the offspring's risk of developing metabolic disease. We will discuss the advantages and challenges of different animal models, the effects of exposure to overnutrition during distinct periods of development, the similarities and differences between and within model systems, and potential mechanisms and future directions in understanding how developmental alterations due to maternal diet exposure influence islet health and function later in life.
健康与疾病的发育起源（DOHaD）假说假定，环境会影响出生后的健康状况，并在疾病病因学中发挥作用。对人类和动物模型的研究均表明，暴露于营养不足或营养过剩环境中会增加日后患代谢性疾病的风险。此外，超重或肥胖母亲所生的后代在儿童期及成年早期更易肥胖，成年后糖耐量也会受损。美国疾病控制与预防中心估计，20岁以上的成年人中有超过70%超重或肥胖，近一半女性在怀孕时超重或肥胖。因此，未来几十年，母亲营养过剩对发育中胎儿的影响可能会更加普遍。本综述将特别关注营养过剩对胰岛发育和功能的影响，以及由此产生的形态和功能变化如何影响后代患代谢性疾病的风险。我们将讨论不同动物模型的优缺点、在发育不同阶段暴露于营养过剩的影响、模型系统之间及内部的异同，以及理解母体饮食暴露导致的发育改变如何影响后期胰岛健康和功能的潜在机制及未来方向。
