The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria, Australia.
Department of Anatomy and Physiology, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Victoria, Australia.
FASEB J. 2022 Jan;36(1):e21981. doi: 10.1096/fj.202100920RR.
The global consumption of highly processed, calorie-dense foods has contributed to an epidemic of overweight and obesity, along with negative consequences for metabolic dysfunction and disease susceptibility. As it becomes apparent that overweight and obesity have ripple effects through generations, understanding of the processes involved is required, in both maternal and paternal epigenetic inheritance. We focused on the patrilineal effects of a Western-style high-fat (21%) and high-sugar (34%) diet (WD) compared to control diet (CD) during adolescence and investigated F0 and F1 mice for physiological and behavioral changes. F0 males (fathers) showed increased body weight, impaired glycemic control, and decreased attractiveness to females. Paternal WD caused significant phenotypic changes in F1 offspring, including higher body weights of pups, increased Actinobacteria abundance in the gut microbiota (ascertained using 16S microbiome profiling), a food preference for WD pellets, increased male dominance and attractiveness to females, as well as decreased behavioral despair. These results collectively demonstrate the long-term intergenerational effects of a Western-style diet during paternal adolescence. The behavioral and physiological alterations in F1 offspring provide evidence of adaptive paternal programming via epigenetic inheritance. These findings have important implications for understanding paternally mediated intergenerational inheritance, and its relevance to offspring health and disease susceptibility.
全球范围内高度加工、高热量食品的消费导致了超重和肥胖的流行，以及代谢功能障碍和疾病易感性的负面后果。随着超重和肥胖通过代际产生连锁反应变得明显，人们需要了解母系和父系表观遗传遗传中涉及的过程。我们专注于与对照组饮食（CD）相比，青春期雄性 Western 高脂肪（21%）和高糖（34%）饮食（WD）的父系效应，并研究了 F0 和 F1 小鼠的生理和行为变化。F0 雄性（父亲）体重增加，血糖控制受损，对雌性的吸引力降低。父系 WD 导致 F1 后代出现明显的表型变化，包括幼崽体重增加、肠道微生物群中放线菌丰度增加（通过 16S 微生物组分析确定）、对 WD 颗粒的食物偏好、雄性优势增加和对雌性的吸引力增加，以及行为绝望减少。这些结果共同证明了父代青春期 Western 饮食的长期跨代影响。F1 后代的行为和生理变化为通过表观遗传遗传进行适应性父系编程提供了证据。这些发现对于理解父系介导的跨代遗传及其与后代健康和疾病易感性的相关性具有重要意义。
