Pre- and postnatal nutrition in sheep affects β-cell secretion and hypothalamic control

Maternal undernutrition increases the risk of type 2 diabetes and metabolic syndrome later in life, particularly upon postnatal exposure to a high-energy diet. However, dysfunctions of, for example, the glucose-insulin axis are not readily detectable by conventional tests early in life, making it difficult to identify individuals at risk. Thus, other methods are required.We hypothesised that prenatally undernourished individuals (but not postnatally overnourished ones) are adapted to a life withlimited food availability, which would be evident under conditions reflecting starvation, stress and short-term abundance of food. In this study, twinpregnant sheep were fed diets meeting 100% (NORM) or50%(LOW) of energy and protein requirements during the last trimester. Twin offspring were fed eithera normal moderate (CONV) diet or a high-carbohydrate-high-fat (HCHF) diet from 3 days to 6 months of age (approximately puberty) and the same moderate diet thereafter until 2 years of age (young adulthood;only females), resultingin four groups:NORM-CONV, LOW-CONV,NORM-HCHF and LOW-HCHF. At the age of 6months and 2 years respectively, they were subjected to fasting and propionate (nutrient abundance)andadrenalinchallenges.At6monthsofage,postnatalHCHF diet exposure caused metabolic alterations, reflecting hypertriglyceridaemia and altered pancreatic β-cell secretion. Irrespective of postnatal diet, prenatal undernutritionwas found to be associated with unexpected endocrine responses of leptin, IGF1 and cortisol during fasting (lackofor theopposite response comparedwiththe controls) in2-year-oldadults. Inconclusion, a HCHF diet interfered with bβ-cell function, whereas maternal undernutrition did notlead to any changes in the LOWoffspring, except to abnormal hormone responses, suggesting that fetal programming interferes with hypothalamic integration of important endocrine axis. © 2013 Society for Endocrinology.