IMPACT OF MATERNAL OBESITY AND DIETARY EXCESS ON FETAL ADIPOSITY

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 孕妇肥胖(MO)是胎儿和新生儿发病率和死亡率的主要原因。妇女孕前母亲体重的增加与后代体重的增加以及身体成分和发育的组织和器官功能的变化导致的持续性和破坏性后果的可能性相关。最近NIDDK和NHLBI RFA承认，为了深入了解MO的生理后果，需要MO的动物模型。我们假设，在绵羊中，MO和可口的肥胖饮食(HPD)：1)增加了从母体到胎儿的脂肪酸运输，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，将血管发育从骨骼肌转移到脂肪组织库中；3)增加了胎儿脂肪到瘦体重，这将导致出生后后代肥胖、胰岛素抵抗和高血压。实验1将描述MO/HPD对胎儿激素水平和胎儿血液和脂肪组织库中脂肪酸的影响，并评估母亲饮食诱导的选定胎儿脂肪库中血管、脂肪酸转运活性和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有关，以及评估供应脂肪组织和骨骼肌的阻力动脉的收缩/松弛特性的变化。试验3将比较饲喂MO/HPD和对照母羊的羔羊的出生后特征，包括羔羊出生体重和形态测量学、肥胖度、生长速度、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. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.