The Sixth Affiliated Hospital of Jinan University, Jinan University, Dongguan, 523560, Guangdong, China.
The Biomedical Translational Research Institute, Faculty of Medical Science, Jinan University, Guangzhou, 510632, Guangdong, China.
Nat Commun. 2022 Feb 9;13(1):768. doi: 10.1038/s41467-022-28469-4.
As a major risk factor to human health, obesity presents a massive burden to people and society. Interestingly, the obese status of parents can cause progeny's lipid accumulation through epigenetic inheritance in multiple species. To date, many questions remain as to how lipid accumulation leads to signals that are transmitted across generations. In this study, we establish a nematode model of C. elegans raised on a high-fat diet (HFD) that leads to measurable lipid accumulation, which can transmit the lipid accumulation signal to their multigenerational progeny. Using this model, we find that transcription factors DAF-16/FOXO and SBP-1/SREBP, nuclear receptors NHR-49 and NHR-80, and delta-9 desaturases (fat-5, fat-6, and fat-7) are required for transgenerational lipid accumulation. Additionally, histone H3K4 trimethylation (H3K4me3) marks lipid metabolism genes and increases their transcription response to multigenerational obesogenic effects. In summary, this study establishes an interaction between a network of lipid metabolic genes and chromatin modifications, which work together to achieve transgenerational epigenetic inheritance of obesogenic effects.
肥胖作为人类健康的主要危险因素，给个人和社会带来了巨大的负担。有趣的是，父母的肥胖状态可以通过多种物种中的表观遗传遗传导致后代的脂质积累。迄今为止，关于脂质积累如何导致跨代传递的信号，仍有许多问题尚未解决。在这项研究中，我们建立了一个线虫模型，即高脂肪饮食（HFD）喂养的秀丽隐杆线虫，这会导致可测量的脂质积累，从而将脂质积累信号传递给它们的多代后代。使用这个模型，我们发现转录因子 DAF-16/FOXO 和 SBP-1/SREBP、核受体 NHR-49 和 NHR-80、以及 delta-9 去饱和酶（fat-5、fat-6 和 fat-7）是跨代脂质积累所必需的。此外，组蛋白 H3K4 三甲基化（H3K4me3）标记脂质代谢基因，并增加它们对多代肥胖效应的转录反应。总之，这项研究建立了一个脂质代谢基因和染色质修饰之间的相互作用网络，它们共同作用实现了肥胖效应的跨代表观遗传遗传。
