PDF(Pubmed)
Abstract：
Maternal obesity, caused by diets rich in fats and sugars during pregnancy, can predispose offspring to metabolic diseases such as diabetes. We hypothesized that obesity during pregnancy leads to increased DNA methylation and reduced protein expression in factors regulating β-cell function and apoptosis. Female C57BL/6J mice were fed a high-fat diet (HFD; 42% fat content; n = 3) or a control diet (CON; 16% fat content; n = 3) for fourteen weeks before and during pregnancy. Offspring were euthanized at 8 weeks and pancreatic tissue was collected. Isolated DNA was analyzed using whole-genome bisulfite sequencing. Protein expression was quantified using LC-MS. No significant differences in body weight were observed between HFD and control pups (p = 0.10). Whole-genome bisulfite sequencing identified 91,703 and 88,415 differentially methylated regions (DMRs) in CON vs. HFD male and female offspring. A total of 34 and 4 proteins were determined to have changes in expression that correlated with changes in DNA methylation in CON vs. HFD males and females, respectively. The majority of these factors were grouped into the metabolic function category via pathway analyses. This study illustrates the complex relationship between epigenetics, diet, and sex-specific responses, therefore offering insights into potential therapeutic targets and areas for further research.
摘要：
产妇肥胖，由怀孕期间富含脂肪和糖的饮食引起的，会使后代易患糖尿病等代谢性疾病。我们假设怀孕期间的肥胖导致调节β细胞功能和凋亡的因子中DNA甲基化增加和蛋白质表达减少。雌性C57BL/6J小鼠在怀孕前和怀孕期间饲喂高脂肪饮食(HFD;42%脂肪含量;n=3)或对照饮食(CON;16%脂肪含量;n=3)14周。在8周时对后代实施安乐死并收集胰腺组织。使用全基因组亚硫酸氢盐测序分析分离的DNA。使用LC-MS定量蛋白质表达。在HFD和对照幼犬之间没有观察到体重的显著差异(p=0.10)。全基因组亚硫酸氢盐测序确定了CON中的91,703和88,415差异甲基化区域（DMRs）与HFD男性和女性后代。确定总共34和4种蛋白质的表达变化与CON和CON中DNA甲基化变化相关。HFD男性和女性，分别。通过途径分析将这些因素中的大多数归入代谢功能类别。这项研究说明了表观遗传学之间的复杂关系，饮食，和性别特异性反应，因此提供对潜在治疗靶点和进一步研究领域的见解。
