Waterland R A, Garza C
Cornell University, Division of Nutritional Sciences, Ithaca, NY 14853, USA.
Am J Clin Nutr. 1999 Feb;69(2):179-97. doi: 10.1093/ajcn/69.2.179.
This review synthesizes a subset of human epidemiologic and experimental animal studies that suggest that early nutrition affects susceptibility to chronic diseases in adulthood. These studies provide evidence that biological mechanisms may exist to "memorize" the metabolic effects of early nutritional environments. However, hypothesis-driven investigations of potential mechanisms have been scant. Thus, our understanding of the biology underlying metabolic imprinting is incomplete. A working definition of metabolic imprinting is proposed, emphasizing the adaptive nature and limited ontogenic window of the mechanisms putatively responsible for these relations. Five specific candidate mechanisms of metabolic imprinting are elaborated: 1) induced variations in organ structure, 2) alterations in cell number, 3) clonal selection, 4) metabolic differentiation, and 5) hepatocyte polyploidization. Last, experimental approaches for probing potential mechanisms with animal models are discussed.
本综述综合了一部分人类流行病学和实验动物研究，这些研究表明早期营养会影响成年后患慢性病的易感性。这些研究提供了证据，表明可能存在生物学机制来“记忆”早期营养环境的代谢影响。然而，对潜在机制的假设驱动研究却很少。因此，我们对代谢印记背后生物学的理解并不完整。本文提出了代谢印记的一个实用定义，强调了假定负责这些关系的机制的适应性本质和有限的个体发生窗口。详细阐述了代谢印记的五种特定候选机制：1）器官结构的诱导性变化，2）细胞数量的改变，3）克隆选择，4）代谢分化，以及5）肝细胞多倍体化。最后，讨论了用动物模型探究潜在机制的实验方法。
