MATERNAL OBESITY, INFLAMMATION AND EPIGENETIC MODIFICATIONS IN FETAL INTESTINE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 近几十年来，肥胖率增加了两倍多。根据NHANES的最新调查(1999-2002年)，20-39岁的非怀孕妇女中有29%患有肥胖症。与此同时，食物过敏和相关的胃肠道粘膜炎症性疾病(GI)也在增加(3.4%的美国人有食物过敏，但3岁以下儿童的比例超过5%)。粘膜免疫系统发育的主要步骤是在胎儿阶段完成的。我们假设母体肥胖(MO)可诱导胎儿胃肠道全身炎症，促进肠道粘膜促炎细胞因子的表达，有利于炎症免疫反应，从而与胃肠道炎症性疾病相关。我们将使用我们成熟的肥胖怀孕绵羊模型-绵羊饲喂100%(CON)或150%的营养需要量(OB)来研究MO对粘膜免疫系统(MIS)发育的影响。由于胚胎发育与人类胚胎的相似性，妊娠绵羊是研究人类妊娠中重要问题的最强大和最广泛使用的胚胎发育模型之一。管理信息系统负责防御胃肠道中大量的细菌和条件致病菌，它们的正确发展对终身健康至关重要。这项研究获得的知识将为干预措施提供目标，以确保适当开发管理信息系统，改善该国越来越多的肥胖者和患有过敏性疾病的人的生活质量。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The obesity rate increased more than 2 fold in recent decades. According to the latest NHANES survey (1999-2002), 29% of non-pregnant women 20-39 years of age are obese. At the same time, food allergy and related mucosal inflammatory diseases in gastrointestinal tract (GI) is also increasing (3.4% of all American have food allergy but more than 5% for children under 3 years old). Major steps of mucosal immune system development are accomplished during the fetal stage. We hypothesize that maternal obesity (MO) induces systemic inflammation in fetal GI tract, which enhances pro-inflammatory cytokine expression in gut mucosa, favoring inflammatory immune response which is associated with GI inflammatory diseases. We will use our well-established obese pregnant sheep model - ewes fed 100% (Con) or 150% of nutrient requirements (OB) to study the effect of MO on mucosal immune system (MIS) development. Due to the similarity of fetal development with the human fetus, pregnant sheep are one of the most powerful and widely used models for fetal development studies that relate to important problems in human pregnancy. MIS is responsible for the defense of tremendous amount of bacteria and opportunistic pathogens in GI tract and their proper development is crucial for lifelong health. Knowledge obtained in this study will provide targets for interventions to ensure proper development of MIS, improving the quality of life for the increasing number of obese people, as well as people suffered by allergic diseases in this country.