Intrauterine Exposure to High Saturated Fat Diet Elevates Risk of Adult-Onset Chronic Dirseases in C57BL/6 Mice

BACKGROUND: The developmental environment 15 thought to determine, in part, lifelong metabolic parameters and risk of adult disease Effects of maternal malnutrition oil fetal growth have been studied extensively, and the role of poor prenatal diet in elevating lifelong, risk of cardiovascular and metabolic disease has been well characterized (www.thebarkertheory.com). However, the contribution of gestational high saturated fat diet (HFD) to adult-onset metabolic disease and skeletal dysfunction has only recently been recognized, and is such is incompletely understood METHODS: The present study evaluates the pathophysiologic mechanisms linking gestational HFD (approximating the macronutrient content of fast food) and elevated oxidative stress (OS) to adult-onset skeletal, cardiovascular, and metabolic dysfunction. RESULTS: Results of this study demonstrate that adult offspring Of dams fed HFD during pregnancy exhibited adult hyperglycemia, insulin resistance, obesity, and hypertension, despite being fed healthy standard rodent chow throughout postnatal life These Offspring also showed significantly lower femoral epiphyseal average bone mineral density (ABMD) at 6 months of age, and dysregulation of distal femoral trabecular architecture it 12 months of age, characteristic of osteoporosis Incidence of these, adult-onset adverse skeletal and metabolic effects was reduced by supplementing the pregnant dam with the antioxidant (quercetin, Q) during pregnancy CONCLUSIONS: Collectively, these data suggest that offspring of dams who consume a diet rich in saturated fats during pregnancy are at increased risk of adult-onset chronic disease Additionally, these chronic diseases were determined to be in-part OS-mediated, and preventable by increasing a prenatal dietary antioxidant, this knowledge offers both a putative mechanism of disease pathogenesis and suggests a potential preventive strategy Birth Defects Res (Part B) 86 377-384, 2009 (C) 2009 Wiley-Liss, Inc.