Tahiri Iasim, Llana Sergio R, Fos-Domènech Júlia, Milà-Guash Maria, Toledo Miriam, Haddad-Tóvolli Roberta, Claret Marc, Obri Arnaud
Neuronal Control of Metabolism Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain.
Heliyon. 2024 Jul 5;10(14):e34043. doi: 10.1016/j.heliyon.2024.e34043. eCollection 2024 Jul 30.
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.
包括肥胖症和糖尿病在内的代谢紊乱在全球造成的负担日益加重，这就需要全面了解其病因，病因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，父亲肥胖通过精子表观遗传修饰成为影响后代代谢健康的一个因素。在本研究中，我们调查了西方饮食诱导的C57BL/6雄性小鼠肥胖对精子染色质可及性及其后代后续代谢健康的影响。利用转座酶可及染色质测序分析，我们在肥胖父亲的精子中发现了450个可及性有差异的区域，这些区域涉及关键的发育和代谢途径。与预期相反，精子中的这些表观遗传改变并不能预测后代的长期代谢紊乱，后代在生命早期仅表现出轻微的短暂代谢变化。F1代雄性和雌性后代均未表现出对肥胖症或糖尿病的持久易感性。这些结果强调了后代对父系表观遗传遗传的生物复原力，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。这项研究呼吁对赋予这种复原力的生物学过程进行进一步研究，这可能为对抗代谢疾病遗传性的干预策略提供信息。
