IMPACT OF MATERNAL OBESITY AND DIETARY EXCESS ON FETAL ADIPOSITY

University Of Wyoming, Laramie WY

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Abstract

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.