Fetal metabolic programing increases the susceptibility of cardiovascular diseases in the offspring due to maternal high-fat-diet during diabetic pregnancy

Increasing trends of obesity in childbearing women with a concurrent gestational diabetes are often associated with adverse fetal metabolic cues. Not only the carbohydrates but also fats are considered to contribute additional dietary fuels to the fetal hearts. To examine the hitherto unknown epigenetic mechanisms on the offspring’s cardiometabolic health due to maternal high-fat (HF) diet (40% kcal) or streptozotocin (STZ)-induced diabetic pregnancy, or both, we carried out an epigenetic characterization of neonatal heart tissue using chromatin immunoprecipitation (ChIP) sequening and a previously validated rat model. Chromatin landscape of offspring’s heart tissue revealed differential peaks distribution on various promoter regions mapped to the rat genome due to histone (H3) modifications by acetylation (H3Ac) or trimethylations of lysine 4 and 27 (H3K4me3 and H3K27me3, respectively). Ongoing evaluations include gene ontology and disease ontology analyses. Together, it is expected that the findings will show that maternal HF-diet with or without gestational diabetes changes the cardiac histone signature in rat offspring, potentially leading to development of novel disease prevention strategies.育龄女性的肥胖率呈持续上升趋势，且合并妊娠糖尿病（gestational diabetes）的育龄女性群体，其胎儿常伴随不良代谢相关信号。不仅碳水化合物，脂肪也被认为可为胎儿心脏提供额外的膳食能量底物。为探究母体高脂（high-fat, HF）膳食（热量占比40%）、链脲佐菌素（streptozotocin, STZ）诱导的糖尿病妊娠，或二者联合作用下，子代心脏代谢健康相关的表观遗传机制（目前尚未明确），本研究采用已验证的大鼠模型，通过染色质免疫共沉淀（chromatin immunoprecipitation, ChIP）测序技术对新生大鼠心脏组织开展表观遗传表征。子代心脏组织的染色质调控图谱显示，由于组蛋白（histone, H3）发生乙酰化（H3Ac）或赖氨酸4、27的三甲基化（分别为H3K4me3与H3K27me3）修饰，大鼠基因组上多个启动子区域出现了差异峰分布。目前正在进行的分析包括基因本体论与疾病本体论分析。综上，本研究预期结果将证实：无论是否合并妊娠糖尿病，母体高脂膳食均会改变大鼠子代的心脏组蛋白修饰谱，有望为新型疾病预防策略的开发提供思路。