191: Changes in visceral adiposity and liver fat in the offspring in a mouse model of pre-pregnancy obesity: a longitudinal study using computed tomography

offspring in a mouse model of pre-pregnancy obesity: a longitudinal study using computed tomography Egle Bytautiene, Nicola Abate, Kathleen Vincent, Igor Patrikeev, Jingna Wei, Massoud Motamedi, George Saade The University of Texas Medical Branch, Obstetrics & Gynecology, Galveston, TX, The University of Texas Medical Branch, Internal Medicine, Galveston, TX, The University of Texas Medical Branch, Center for Biomedical Engineering, Galveston, TX OBJECTIVE: The epidemiology of the fetal origin of adult diseases, including obesity, diabetes, and hypertension, has been well established but the mechanisms remain to be determined. The objective of this study was to evaluate the sequence of change in postnatal visceral adiposity and fatty liver infiltration using a previously validated mouse model of developmental programming of metabolic syndrome (MetS) induced by maternal pre-pregnancy obesity. STUDY DESIGN: CD-1 female mice were placed on standard (SF) or high fat diet (HF) starting 3 months before mating. After weaning, their offspring were placed on SF diet. The offspring (males: SF n 7, HF n 8; females: SF n 9, HF n 7) were weighed and imaged using a micro-computed tomography (CT) scanner monthly from 1 until 6 months of age. CT images were used to longitudinally evaluate visceral adipose tissue (VAT), measured as percent VAT area to total body area at the L5 vertebrae level, and fat infiltration in the liver, measured as the ratio of spleen/liver radiodensity. Data were analyzed by maternal diet and gender using 2-way ANOVA (significance: P 0.05). RESULTS: There were no significant differences in either male or female total body weights between SF and HF groups until 6 months of age when the HF offspring became heavier (P 0.05 in both genders). Significantly higher VAT was seen in both genders in the HF compared to SF group starting at 3 months of age (Figure, females P 0.05 at 3, 5, 6 months, and P 0.01 at 4 months, males P 0.001 3 thru 6 months). Significant fat infiltration into the liver was detected in HF female offspring starting at 4 month of age (P 0.01 at 4, P 0.05 at 5, and P 0.001 at 6 months) and in HF males offspring starting at 3 months (P 0.05 at 3 and 6, P 0.001 at 4, and P 0.01 at 6 months). CONCLUSION: Abnormal visceral adiposity and fatty liver infiltration occur prior to any change in body weight in this animal model of developmental programming of MetS. This non-invasive approach may assist in early detection of offspring at risk of MetS, and application of postnatal age-specific interventions to prevent its long term consequences. 192 Adipose tissue dysfunction in a model of developmental programming of metabolic syndrome Egle Bytautiene, Debdeep Banerjee, Talar Kechichian, Huaizhi Yin, Elena Sbrana, Esther Tamayo, Nicola Abate, George R. Saade The University of Texas Medical Branch, Obstetrics & Gynecology, Galveston, TX, The University of Texas Medical Branch, Internal Medicine, Galveston, TX OBJECTIVE: Obesity is characterized by adipose tissue accumulation, which in turn is associated with metabolic consequences. Distribution, type, and function of adipose tissue accumulation are believed to be more important than overall change in body or fat mass. The objective of this study was to investigate whether visceral adipose tissue dysfunction is present in a previously validated mouse model of developmental programming of metabolic syndrome. STUDY DESIGN: CD-1 female mice were placed on standard (SF) or high fat (HF) diet starting 3 months before mating, and continued during pregnancy and weaning. The offspring were placed on SF diet after weaning. At 6 months of age, the offspring were euthanized and tissues collected. mRNA expression of hypoxia-inducible factor 1 (HIF-1 )and transforming growth factor 3 (TGF 3), and protein expressions of angiotensin (ANG) and its receptors, angiotensin receptor 1 and 2 (AT1 and AT2, respectively), in adipose tissue and kidney were determined using quantitative real time RT-PCR and Western blot (SF n 10-14, HF n 8-10). Results were analyzed using Students t-test (significance: P 0.05). RESULTS: HIF-1 mRNA expression was significantly increased in adipose tisssue from HF offspring compared to SF group (P 0.04), with no significant differences in TGF 3 mRNA expression. ANG protein expression was significantly higher and AT2 was significantly lower in adipose tissue from offspring born to HF mothers as compared to SF group (Figure). There were no significant differences in the expression of HIF-1 ;, TGF 3, ANG, AT1 and AT2 in the kidneys between the 2 offspring groups. CONCLUSION: Maternal pre-pregnancy obesity from high fat diet predisposes the offspring for adipose tissue dysfunction later in life. The altered adipose tissue function can then lead to a number of cascade events involved in the developmental origin of adult hypertension and metabolic syndrome. www.AJOG.org Clinical Obstetrics, Medical-Surgical-Disease, Neonatology, Physiology-Endocrinology Poster Session I