Long-Term Consequences of Maternal and Neonatal Nutrition for Pregnancy and Postnatal Outcomes

Abstract Text: The nutritional environment during fetal and neonatal life is a key determinant affecting the risk for adult-onset diseases, such as diabetes and obesity. Studies show that preterm infants experience increased risk for glucose intolerance as adolescents and young adults. Preterm infants often receive parenteral nutrition for several days or weeks after birth as a lifesaving form of clinical support. Considerable evidence shows that the normal and dysfunctional secretion of gut hormones plays a key role in metabolic health and diseases, including diabetes and obesity.  We have used the model of parenterally fed neonatal pig to test whether the modality of nutritional support (enteral vs. parenteral) significantly impacts both the pattern of gut hormone secretion and metabolic function.  We first showed (J. Nutr.140:2193) that chronic parenteral (PN) compared to enteral (EN) nutrition in neonatal pigs for two weeks leads to an adverse metabolic phenotype marked by increased glucose intolerance, insulin resistance, body fat deposition and reduced pancreatic beta-cell proliferation.  We also showed (JPEN.36:538) that pattern of enteral nutrition (intermittent vs. continuous) is a stronger determinant than modality of nutrition to optimize glucose utilization and insulin sensitivity.  We also showed that the secretion of gut incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) correlated closely with glucose utilization and insulin sensitivity.  An important question is whether the adverse metabolic phenotype that results from that chronic parenteral (PN) during the first two weeks of neonatal life persists into late infancy and adolescence.  We recently tested this in newborn pigs by feeding either PN or EN for 2 wk followed by ad lib feeding of a high-fat (30%) and sucrose (20%) diet for 5 mon. We measured body composition by dual-emission X-ray absorptiometry at 2 wk, 8 wk, and 5 mon and performed an IVGTT at 5 mon.   Our results show that PN during the neonatal period increased adiposity transiently into early infancy but PN-induced glucose intolerance, adiposity, pancreatic beta cell number and hepatic steatosis were not sustained into adolescence even when challenged with an obesogenic diet.  This presentation will highlight the link between enteral nutrition as a key trigger for gut hormone secretion and function and how these hormone signaling pathways made be relevant to domestic animal growth.

Keywords: nutrition, pregnancy, signaling pathways