Oral Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

Programming metabolic and psychiatric diseases: Effects of poor maternal diet and Health (#139)

Kevin Grove 1
  1. OHSU, Beaverton, OR, United States

Childhood obesity is associated with increased risk of metabolic diseases later in life; however, it is also associated with a broad spectrum of behavior/psychological disorders including depression, anxiety, poor learning, and attention deficient disorder.  Maternal obesity, diabetes and consumption of a western-style diet (WSD; high in fats and calories) during pregnancy has a high association with early onset obesity in children.  Using a nonhuman primate (NHP) model our group is investigating the relative impact of maternal metabolic health and diet on the development of hypothalamic systems involved in the regulation of energy homeostasis as well as stress and anxiety behaviors. To date, we have observed that fetal offspring of animals consuming the HFD develop early onset fatty liver as well as abnormalities in the development of pancreatic islets and in brain circuits involved in the regulation of appetite and stress responsiveness.  A likely causal factor for these developmental abnormalities is placental insufficiency and an increase in circulating cytokines (originating from the placenta) during critical periods of fetal development, as well as the activation of local inflammatory systems within the brain.  Importantly, most of these developmental programming effects were independent of the maternal metabolic phenotype, as they were observed in both obese and lean animals consuming the WSD.  Infant offspring of animals consuming the WSD have a higher rate of growth during the postnatal period resulting in a doubling of body fat and insulin resistance, as well as pancreatic islet hyperplasia and fatty liver at weaning.  Furthermore, female, but not male, infant offspring also display increased anxiety-like behavior.  This sexual dimorphism in anxiety-like behavior is consistent with human clinical studies demonstrating that the behavior/psychological disorders associated with childhood obesity are more prevalent in young girls.  However, both male and female WSD offspring displayed increased appetite, food preferences for palatable foods and social behavior abnormalities, that were not reversible by post-weaning diet reversal.  Overall, these results suggest that chronic consumption of a WSD during pregnancy alone can cause significant abnormalities in the development of critical metabolic system in the fetal offspring.  Many of the changes appear to be due to the high lipid environment leading to the activation of the proinflammatory cytokines both within the placenta as wells as the brain.  This lipotoxicity may also have broad negative impact on the neural systems involved in social behavior as well as learning and memory.  Acknowledgements: NIH grants DK79194, DK090954 and OD011092.