Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, Exeter High School, 1 Blue Hawk Drive, Exeter, NH 03833, USA.
Nutrients. 2019 Sep 3;11(9):2075. doi: 10.3390/nu11092075.
Obesity and metabolic disease present a danger to long-term health outcomes. It has been hypothesized that epigenetic marks established during early life might program individuals and have either beneficial or harmful consequences later in life. In the present study, we examined whether maternal diet alters DNA methylation and whether such modifications persist after an obesogenic postnatal dietary challenge. During gestation and lactation, male Sprague-Dawley rats were exposed to either a high-fat diet (HF; = 10) or low-fat diet (LF; = 10). After weaning, all animals were fed a HF diet for an additional nine weeks. There were no differences observed in food intake or body weight between groups. Hepatic DNA methylation was quantified using both methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylation-sensitive restriction enzyme sequencing (MRE-seq). Overall, 1419 differentially methylated regions (DMRs) were identified. DMRs tended to be located in CpG shores and were enriched for genes involved in metabolism and cancer. Gene expression was measured for 31 genes in these pathways. and were confirmed to be differentially expressed. Finally, we attempted to quantify the functional relevance of intergenic DMRs. Using chromatin contact data, we saw that conserved DMRs were topologically associated with metabolism genes, which were associated with differential expression of , , and . We show that although maternal dietary fat is unable to reverse offspring weight gain in response to a postnatal obesogenic diet, early life diet does program the hepatic methylome. Epigenetic alterations occur primarily in metabolic and cancer pathways and are associated with altered gene expression, but it is unclear whether they bear consequence later in life.
肥胖和代谢性疾病对长期健康结果构成威胁。人们假设，生命早期建立的表观遗传标记可能会对个体进行编程，并在以后的生活中产生有益或有害的后果。在本研究中，我们研究了母体饮食是否会改变 DNA 甲基化，以及这种修饰是否在肥胖的产后饮食挑战后仍然存在。在妊娠和哺乳期，雄性 Sprague-Dawley 大鼠分别暴露于高脂肪饮食（HF；n = 10）或低脂肪饮食（LF；n = 10）中。断奶后，所有动物都额外喂食高脂肪饮食 9 周。各组之间的食物摄入量或体重无差异。使用甲基化 DNA 免疫沉淀测序（MeDIP-seq）和甲基敏感限制性内切酶测序（MRE-seq）定量肝 DNA 甲基化。总体而言，鉴定出 1419 个差异甲基化区域（DMR）。DMR 倾向于位于 CpG 海岸，并且富含参与代谢和癌症的基因。这些途径中的 31 个基因的表达进行了测量。和被证实存在差异表达。最后，我们试图量化基因间 DMR 的功能相关性。使用染色质接触数据，我们发现保守的 DMR 与代谢基因拓扑相关，这与、和的差异表达相关。我们表明，尽管母体饮食脂肪不能逆转后代对产后肥胖饮食的体重增加，但早期生活饮食确实会对肝甲基组进行编程。表观遗传改变主要发生在代谢和癌症途径中，并与改变的基因表达相关，但尚不清楚它们是否会对以后的生活产生影响。
