MATERNAL OBESITY AND DEVELOPMENT OF TYPE 1 DIABETES IN NOD MICE OFFSPRING

母体肥胖与 NOD 小鼠后代 1 型糖尿病的发生

• 批准号: 8167816
• 负责人: Meijun Zhu
• 金额: $ 3.1万
• 依托单位: UNIVERSITY OF WYOMING
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167816
• 关键词: MATERNAL; OBESITY; DEVELOPMENT; TYPE; DIABETES

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. According to the latest NHANES survey (1999-2002), 29% of women at childbearing age (20-39 years old) are obese. At the same time, autoimmune diseases including Type I diabetes are also increasing, indicating a likely link between maternal obesity (MO) and altered immune system development. Major components of immune system development are accomplished during the fetal and neonatal stages. Our preliminary data show that MO led to systemic inflammation in fetuses and the expression of toll like receptor (TLR) 4 was elevated. We hypothesized that MO induces systemic inflammation in fetus, which promotes survival of thymocytes specific to host-derived antigens, increasing the incidence of autoimmune diseases including type I diabetes in offspring. We are using well-established non-obese diabetic (NOD) mice fed control (Con) or obesogenic (OB) diet to study the effect of MO on the incidences of offspring type I diabetes. We also utilize TLR4 knockout mice to study the role of TLR4 in the fetal immune system development. Based on the data obtained from this study, the PI will further explore mechanisms associated with the fetal immune system development and immune tolerance, and develop specific strategies to cope with autoimmune diseases. Knowledge obtained in this study will provide targets for interventions to ensure the proper development of the immune system, improving the quality of life for the offspring of the increasing number of obese pregnant women in this country.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 根据最新的国家健康和营养状况调查（1999-2002年），29%的育龄妇女（20-39岁）肥胖。与此同时，包括I型糖尿病在内的自身免疫性疾病也在增加，这表明母体肥胖（MO）与免疫系统发育改变之间可能存在联系。免疫系统发育的主要组成部分在胎儿和新生儿阶段完成。我们的初步数据表明，MO导致胎儿全身炎症和Toll样受体（TLR）4的表达升高。我们假设MO诱导胎儿全身性炎症，这促进了对宿主衍生抗原特异性的胸腺细胞的存活，增加了后代自身免疫性疾病包括I型糖尿病的发病率。我们正在使用良好建立的非肥胖糖尿病（NOD）小鼠喂养对照（Con）或致肥胖（OB）饮食，以研究MO对后代I型糖尿病发病率的影响。我们还利用TLR 4基因敲除小鼠来研究TLR 4在胎儿免疫系统发育中的作用。 基于本研究获得的数据，PI将进一步探索与胎儿免疫系统发育和免疫耐受相关的机制，并制定科普自身免疫性疾病的具体策略。这项研究中获得的知识将为干预措施提供目标，以确保免疫系统的正常发育，提高该国越来越多肥胖孕妇后代的生活质量。