IMPACT OF MATERNAL OBESITY AND DIETARY EXCESS ON FETAL ADIPOSITY

该子项目是利用 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来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 母亲肥胖是导致胎儿和新生儿发病和死亡的主要原因。妇女怀孕前母体体重的增加与后代体重的增加以及身体组成和发育中的组织和器官功能的变化造成的持久和破坏性后果的可能性有关。最近的NIDDK和NHLBI RFA承认，需要MO的动物模型来深入了解生理后果。我们假设MO和高适口性致肥胖饮食（HPD）在绵羊中：1）增加脂肪酸从母体向胎儿隔室的转运，导致胎儿脂肪沉积增加，2）通过血管生成和血管反应性的改变使血管发育远离骨骼肌向脂肪组织库转移，3）增加胎儿脂肪至瘦体重，这将导致肥胖，胰岛素抵抗和高血压。实验1将描述MO/HPD对胎儿血液和脂肪组织库中胎儿激素水平和脂肪酸谱的影响，并评价母体饮食诱导的血管分布、脂肪酸转运活性和选定胎儿脂肪库中脂肪细胞特征的变化。实验2将确定MO/HPD对胎儿脂肪和骨骼肌组织血管生成因子/受体活性的影响，并将这些数据与比较血管分布相关，以及评价供应脂肪组织和骨骼肌的阻力动脉的收缩/舒张特性的变化。实验3将比较MO/HPD和对照饲养母羊所生羔羊的出生后特征，包括羔羊出生体重和形态测量学、肥胖、生长速率、激素分泌谱、胰岛素抵抗和3岁时的血压。

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. Maternal obesity (MO) is a major cause if fetal and neonatal morbidity and mortality. Increased pre-pregnancy maternal weight in women correlates with increased offspring weight and the potential for persistent and damaging consequences resulting from changes in body composition and developing tissue and organ function. A recent NIDDK and NHLBI RFA acknowledges that animal models of MO are needed to gain insight into the physiologic consequences. We hypothesize that MO and a highly palatable obesogenic diet (HPD) in sheep: 1) increases fatty acid transport from the maternal to the fetal compartment resulting in increased fetal fat deposition, 2) shifts vascular development away from skeletal muscle towards adipose tissue depots through alterations in angiogenesis and vascular reactivity, 3) increases fetal fat to lean body mass which will result in obesity, insulin resistance and hypertension in offspring in postnatal life. Experiment 1 will characterize the impacts of MO/HPD on fetal hormone levels and fatty acid profiles in fetal blood and adipose tissue depots, and evaluate maternal diet-induced changes in vascularity, fatty acid transport activity and adipocyte characteristics in selected fetal fat depots. Experiment 2 will determine the Impact of MO/HPD on fetal adipose and skeletal muscle tissue angiogenic factor/receptor activity and relate these data to comparative vascularity, as well as evaluate alterations in the contractile/relaxant properties of resistance arteries supplying adipose tissue and skeletal muscle. Experiment 3 will compare postnatal characteristics of lambs born to MO/HPD and Control fed ewes, including lamb birth weight and morphometrics, adiposity, growth rate, hormone secretion profiles, insulin resistance and blood pressures to 3 years of age.