We have developed a sheep model to facilitate studies of the fetal programming effects of mismatched perinatal and postnatal nutrition. During the last trimester of gestation, twenty-one twin-bearing ewes were fed a normal diet fulfilling norms for energy and protein (NORM) or 50 % of a normal diet (LOW). From day 3 postpartum to 6 months (around puberty) of age, one twin lamb was fed a conventional (CONV) diet and the other a high-carbohydrate -high-fat (HCHF) diet, resulting in four groups of offspring: NORM-CONV; NORM-HCHF; LOW-CONV; LOW-HCHF. At 6 months of age, half of the lambs (all males and three females) were slaughtered for further examination and the other half (females only) were transferred to a moderate sheep diet until slaughtered at 24 months of age (adulthood). Maternal undernutrition during late gestation reduced the birth weight of LOW offspring (P, 0·05), and its long-term effects were increased adrenal size in male lambs and adult females (P, 0·05), increased neonatal appetite for fat-(P¼0·004) rather than carbohydrate-rich feeds (P,0·001) and reduced deposition of subcutaneous fat in both sexes (P,0·05). Furthermore, LOW-HCHF female lambs had markedly higher visceral:subcutaneous fat ratios compared with the other groups (P, 0·001). Postnatal overfeeding (HCHF) resulted in obesity (. 30 % fat in soft tissue) and widespread ectopic lipid deposition. In conclusion, our sheep model revealed strong pre-and postnatal impacts on growth, food preferences and fat deposition patterns. The present findings support a role for subcutaneous adipose tissue in the development of visceral adiposity, which in humans is known to precede the development of the metabolic syndrome in human adults.

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 with limited 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) or 50% (LOW) of energy and protein requirements during the last trimester. Twin offspring were fed either a 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), resulting in four groups: NORM-CONV, LOW-CONV, NORM-HCHF and LOW-HCHF. At the age of 6 months and 2 years respectively, they were subjected to fasting and propionate (nutrient abundance) and adrenalin challenges. At 6 months of age, postnatal HCHF diet exposure caused metabolic alterations, reflecting hypertriglyceridaemia and altered pancreatic b-cell secretion. Irrespective of postnatal diet, prenatal undernutrition was found to be associated with unexpected endocrine responses of leptin, IGF1 and cortisol during fasting (lack of or the opposite response compared with the controls) in 2-year-old adults. In conclusion, a HCHF diet interfered with b-cell function, whereas maternal undernutrition did not lead to any changes in the LOW offspring, except to abnormal hormone responses, suggesting that fetal programming interferes with hypothalamic integration of important endocrine axis.