Feast or famine: Altered maternal nutrition and disease risk in offspring

Abstract

Significant alterations in maternal nutrition may induce long-term metabolic consequences in offspring, in particular obesity and features characteristic of the metabolic syndrome. Although maternal nutrient deprivation has been well characterized in this context, little is known regarding the effects of maternal high fat (HF) nutrition on offspring. Methods: The present study investigated the impact of two animal models of altered maternal nutrition on offspring metabolic phenotype: A) maternal calorie restriction, whereby pregnant dams were exposed to 50% undernutrition compared to controls during pregnancy, lactation or both, and B) maternal HF diet either pre-conceptionally and throughout pregnancy and lactation, or throughout pregnancy and lactation alone. Further, to examine the interaction between pre- and post-weaning diets on growth and metabolic outcomes, offspring were weaned onto either control or HF nutrition. Weight gain and body composition were recorded in mothers and offspring, and at postnatal day 180 blood and pancreata were collected from offspring. Importantly, both male and female offspring were examined to determine possible sex-specific altered susceptibility to metabolic disease. Maternal undernutrition imposed at different developmental windows resulted in offspring effects that were sex- and window dependant. Undernutrition during pregnancy alone, particularly when offspring were fed an unrestrained postnatal diet, resulted in offspring with increased adiposity and altered leptin sensitivity. Prevention of catch-up growth during lactation ameliorated the adverse metabolic effects associated with gestational undernutrition, particularly in females. Adult offspring born to dams fed a HF diet during pregnancy and lactation, with or without a preconceptional HF diet, had similar obesogenic phenotypes, irrespective of post-weaning diet. This suggested that pre-conceptional obesity did not induce a phenotype different from the obesogenic diet during pregnancy and lactation alone. However, offspring of HF-fed mothers displayed differential pancreatic expression patterns of key genes in insulin and leptin signalling pathways, dependent on the window of exposure to the maternal obesogenic diet. Conclusions: This study has provided novel insights into the differential effects of early life nutritional adversity during different critical windows of developmental plasticity on offspring growth and pancreatic leptin and insulin signalling. Possible mechanisms are discussed, together with a critique of the predictive adaptive responses hypothesis and the possible adverse impact of catch-up growth.