Fetal programming of obesity and metabolic dysregulation by maternal nutrition

Increased risk for obesity and metabolic disease has been attributed to both maternal overnutrition and undernutrition in pregnancy. Obesity and metabolic disease are components of the metabolic syndrome which predisposes to development of more severe disease, including cardiovascular disease and type II diabetes. This dissertation discusses studies using a sheep model to evaluate the effects of maternal overnutrition on fetal development and maternal undernutrition on offspring disease risk. In the first experiment, ewes were fed to achieve normal weight, overweight or obesity prior to and during pregnancy. The most overfed ewes became fattest by the time of breeding which was associated with increased fetal adiposity and organ growth at mid-gestation. In the second experiment, aged ewe offspring born from mothers nutrient restricted in early gestation were evaluated for differences in feeding behavior, glucose-insulin dynamics and body composition during a bout of ad libitum feeding. These aged (6 yrs) ewe offspring of nutrient restricted mothers demonstrated greater and more rapid feed intake, greater body weight gain and gain efficiency, as well as lower insulin sensitivity and higher insulin secretion than control ewe offspring. In the third experiment, these same aged ewe offspring from nutrient restricted dams showed lower progesterone concentrations throughout the estrous cycle, a result previously observed in these ewes at one and two years of age, indicating progesterone levels have been permanently programmed in these ewes. Overall, fetal programming of disease risk related to metabolic disease and obesity has been demonstrated in our ewe model of both maternal under- and overnourishment.