Fetal programming: Maternal fructose consumption, exercise and gestational weight gain

Emily J Arentson, Purdue University

Abstract

The central hypothesis of this dissertation is that modifiable lifestyle factors during pregnancy and novel models of fetal programming, namely fructose consumption, exercise and gestational weight gain, alter the early life environment and modulate offspring risk for aspects of metabolic syndrome. Furthermore, we hypothesize a post-weaning diet can further precipitate offspring risk for metabolic syndrome. In particular we were interested in programming in small intestine as a result of the early life environment Therefore, the objectives of this work were first to determine how maternal fructose and low protein consumption during pregnancy and lactation program offspring and also to determine the interaction with the post-weaning diet. Secondly, our objective was to determine the effects of aerobic exercise training during pregnancy on metabolic programming of the offspring. Thirdly, our objective was to determine the effect of excess maternal gestational weight gain on offspring and also to determine the interaction of maternal weight gain with the post-weaning diet on offspring. Pregnant rats were fed a control, high fructose or low protein diet during pregnancy and lactation. Male offspring were weaned onto a control, high fat or high fructose diet for 15 weeks. These data show offspring of fructose and low protein fed dams exhibit impaired growth. Weaned offspring of fructose fed dams onto a high fat diet displayed impaired glucose tolerance. Furthermore, offspring demonstrated a persistent adaptive response for intestinal gene expression at 18 weeks of age that is dependent on maternal background. Our data suggest that intestine of offspring from fructose fed dams possesses greater metabolic flexibility than offspring of low protein fed dams. Intestine of offspring from protein restricted dams alter basal transcript levels of transporters and key metabolic-related transcripts and therefore appear to adapt to conserve energy, but retain ability to increase these in response to diet. Pregnant cross-breed commercial gilts were exercised on a treadmill for 30-45 minutes per day, 5 days a week at 65 -85% of maximal heart rate or allowed normal activity level for the duration of gestation up to one week pre-parturtum. These data indicated that although maternal weight gain was attenuated by exercise, offspring birth weight and weight at 12 weeks of age were not altered. Analyses of regulators of metabolic flux indicated that small intestine was immediately responsive to maternal exercise in offspring at 48 h of age and displayed an increased capacity for oxidation. However, at 12 weeks of intestine in offspring exercised dams no longer maintained the enhanced capacity for oxidation. Offspring from crossbred gilts fed a normal or a high energy diet to induce a 30% increase in gestation weight gain were weaned to either a normal or high energy diet. These data indicate that offspring from sows that gained excess weight during pregnancy tended to weigh more. Small intestine of 12 week old offspring of sows that gained excess weight exhibited a reduced capacity for fatty acid oxidation. Furthermore, 12 week old offspring of sows that gained excess weight that were weaned on to a high energy post-weaning diet displayed increased fasting glucose and insulin, which are indicators of metabolic syndrome. Together these data indicate that maternal fructose and low protein consumption and excess gestational weight gain program offspring in combination with a high fat post-weaning diet modulate offspring risk for metabolic syndrome. Maternal exercise may modulate offspring risk for disease in later life by increasing oxidative capacity of young offspring. Furthermore, changes in offspring risk for metabolic disease may be contributed in part by changes in small intestine which we have shown to be responsive to the early life environment. (Abstract shortened by UMI.)

Degree

Ph.D.

Advisors

Buhman, Purdue University.

Subject Area

Animal sciences|Nutrition

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