Department of Fisheries, Veterinary, and Animal Science, University of Rhode Island, 45 Upper College Rd., Kingston, RI 02881, USA.
Int J Mol Sci. 2024 Jul 3;25(13):7317. doi: 10.3390/ijms25137317.
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 ( = 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.
母体肥胖是由孕期高脂肪、高糖饮食引起的，可使后代易患糖尿病等代谢疾病。我们假设孕期肥胖会导致调节β细胞功能和细胞凋亡的因子中 DNA 甲基化增加和蛋白表达减少。雌性 C57BL/6J 小鼠在怀孕前和怀孕期间分别喂食高脂肪饮食（HFD；脂肪含量 42%；n = 3）或对照饮食（CON；脂肪含量 16%；n = 3）14 周。后代在 8 周时被安乐死，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。HFD 和对照幼崽之间的体重没有显著差异（ = 0.10）。全基因组亚硫酸氢盐测序确定了 CON 与 HFD 雄性和雌性后代之间的 91703 和 88415 个差异甲基化区域（DMR）。在 CON 与 HFD 雄性和雌性中，共有 34 个和 4 个蛋白的表达变化与 DNA 甲基化变化相关。这些因子中的大多数通过途径分析被归类为代谢功能类别。本研究说明了表观遗传学、饮食和性别特异性反应之间的复杂关系，因此为潜在的治疗靶点和进一步研究提供了思路。
