Transgenerational inheritance of metabolic disease.
Transgenerational inheritance of metabolic disease.
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DOI：
10.1016/j.semcdb.2015.04.007
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发表时间：
2015-07
影响因子：
7.3
通讯作者：
Buchner DA
中科院分区：
文献类型：
--
作者：
Stegemann R;Buchner DA
代谢性疾病包括几种疾病，包括肥胖、2型糖尿病和血脂异常。最近，代谢性疾病的发病率急剧增加，主要是由于全球肥胖流行。跨代遗传仍然存在争议，但基于越来越多的模式生物（从秀丽隐杆线虫到m.s musus到S. scrofa）的原理验证研究，已经提出了对人类代谢性疾病风险的贡献。总的来说，这些研究表明，在没有持续暴露于触发刺激的情况下，遗传风险是在几代人中从父母遗传给后代的表观遗传。各种各样的初始触发因素可以诱导跨代遗传，包括高脂肪或高糖饮食、低蛋白饮食、各种毒素和祖先遗传变异。尽管疾病风险跨代遗传的机制基础在很大程度上仍然未知，但推测介导传播的分子包括小rna、组蛋白修饰和DNA甲基化。由于代谢性疾病对人类健康的影响相当大，因此更好地了解代谢性疾病风险跨代遗传的作用，为治疗干预开辟新的途径，改进现有的临床诊断和治疗方法至关重要。
Metabolic disease encompasses several disorders including obesity, type 2 diabetes, and dyslipidemia. Recently, the incidence of metabolic disease has drastically increased, driven primarily by a worldwide obesity epidemic. Transgenerational inheritance remains controversial, but has been proposed to contribute to human metabolic disease risk based on a growing number of proof-of-principle studies in model organisms ranging from C. elegans to M. musculus to S. scrofa. Collectively, these studies demonstrate that heritable risk is epigenetically transmitted from parent to offspring over multiple generations in the absence of a continued exposure to the triggering stimuli. A diverse assortment of initial triggers can induce transgenerational inheritance including high-fat or high-sugar diets, low-protein diets, various toxins, and ancestral genetic variants. Although the mechanistic basis underlying the transgenerational inheritance of disease risk remains largely unknown, putative molecules mediating transmission include small RNAs, histone modifications, and DNA methylation. Due to the considerable impact of metabolic disease on human health, it is critical to better understand the role of transgenerational inheritance of metabolic disease risk to open new avenues for therapeutic intervention and improve upon the current methods for clinical diagnoses and treatment.