PDF(Pubmed)
Abstract：
The increasing global burden of metabolic disorders including obesity and diabetes necessitates a comprehensive understanding of their etiology, which not only encompasses genetic and environmental factors but also parental influence. Recent evidence has unveiled paternal obesity as a contributing factor to offspring\'s metabolic health via sperm epigenetic modifications. In this study, we investigated the impact of a Western diet-induced obesity in C57BL/6 male mice on sperm chromatin accessibility and the subsequent metabolic health of their progeny. Utilizing Assay for Transposase-Accessible Chromatin with sequencing, we discovered 450 regions with differential accessibility in sperm from obese fathers, implicating key developmental and metabolic pathways. Contrary to expectations, these epigenetic alterations in sperm were not predictive of long-term metabolic disorders in offspring, who exhibited only mild transient metabolic changes early in life. Both male and female F1 progeny showed no enduring predisposition to obesity or diabetes. These results underscore the biological resilience of offspring to paternal epigenetic inheritance, suggesting a complex interplay between inherited epigenetic modifications and the offspring\'s own developmental compensatory mechanisms. This study calls for further research into the biological processes that confer this resilience, which could inform interventional strategies to combat the heritability of metabolic diseases.
摘要：
包括肥胖和糖尿病在内的代谢紊乱的全球负担不断增加，因此需要对其病因进行全面了解。这不仅包括遗传和环境因素，还包括父母的影响。最近的证据表明，父系肥胖是通过精子表观遗传修饰导致后代代谢健康的一个因素。在这项研究中,我们研究了西方饮食诱导的C57BL/6雄性小鼠肥胖对精子染色质可及性及其后代代谢健康的影响.利用转座酶可访问染色质的测序分析，我们发现了450个肥胖父亲精子可及性不同的区域，涉及关键的发育和代谢途径。与预期相反,这些精子的表观遗传改变并不能预测后代的长期代谢紊乱，在生命早期仅表现出轻微的短暂代谢变化。雄性和雌性F1后代均未显示出肥胖或糖尿病的持久倾向。这些结果强调了后代对父系表观遗传的生物复原力，表明遗传的表观遗传修饰与后代自身的发育补偿机制之间存在复杂的相互作用。这项研究要求进一步研究赋予这种弹性的生物过程，这可以提供干预策略来对抗代谢性疾病的遗传性。
