Junien Claudine
Inserm Unit 383, Clinique Maurice Lamy, porte 15, Hôpital Necker- Enfants Malades, 149 rue de Sèvres, 75743, Paris, France.
J Inherit Metab Dis. 2006 Apr-Jun;29(2-3):359-65. doi: 10.1007/s10545-006-0299-7.
Specific, often unbalanced diets are used to circumvent the metabolic defects of patients with monogenic inborn errors of metabolism. Human epidemiological studies and appropriately designed dietary interventions in animal models have provided considerable evidence to suggest that nutritional imbalance and metabolic disturbances, during critical time windows of developmental programming, may have a persistent effect on the health of the child and later in adulthood. Thus patients with monogenic inborn errors of metabolism may also suffer additional types of alterations due to the lack or excess of key nutrients. Interactions of nutrients with the epigenetic machinery lead to epigenetic changes associated with chromatin remodelling and regulation of gene expression that underlie the developmental programming of pathological consequences in adulthood. Today, with the explosion of new technologies, we can explore on a large scale the effects of nutrients on the level of expression of thousands of expressed genes (nutritional genomics and epigenomics), the corresponding protein products and their posttranslationally modified derivatives (proteomics), and the host of metabolites (metabolomics) generated from endogenous metabolic processes or exogenous dietary nutrients and can establish the relationship between these biological entities and diet, health or disease. The combination of these various lines of research on epigenetic programming processes should highlight new strategies for the prevention and treatment of inborn errors of metabolism.
特定的、通常不均衡的饮食被用于规避患有单基因先天性代谢缺陷患者的代谢缺陷。人类流行病学研究以及在动物模型中进行的精心设计的饮食干预提供了大量证据，表明在发育编程的关键时间窗口期间，营养失衡和代谢紊乱可能会对儿童及成年后的健康产生持续影响。因此，患有单基因先天性代谢缺陷的患者也可能因关键营养素的缺乏或过量而遭受其他类型的改变。营养素与表观遗传机制的相互作用会导致与染色质重塑和基因表达调控相关的表观遗传变化，这些变化是成年期病理后果发育编程的基础。如今，随着新技术的迅猛发展，我们能够大规模探索营养素对数千个表达基因（营养基因组学和表观基因组学）的表达水平、相应的蛋白质产物及其翻译后修饰衍生物（蛋白质组学）以及内源性代谢过程或外源性饮食营养素产生的大量代谢物（代谢组学）的影响，并能够建立这些生物实体与饮食、健康或疾病之间的关系。这些关于表观遗传编程过程的不同研究方向的结合，应该会凸显出预防和治疗先天性代谢缺陷的新策略。
