Presented at the Neonatal Society 2005 Autumn Meeting.
Gardner DS, Sinclair KD, Symonds ME
Centre for Reproduction and Early Life, School of Human Development, University Hospital, Nottingham, UK
Introduction: Obesity is becoming the major health burden facing westernised societies. Excess adipose tissue mass, specifically ‘centripetal’ i.e. around the abdomen, increases the risk of a range of adverse health outcomes. Adult total adiposity is influenced by the prenatal diet, but preliminary data in animal models suggest regional adiposity is not. However in sheep, at least, there appears a defined window of time in which regional adipose tissue deposition is organised and thereafter remains unchanged. This largely occurs during the lactation period. In this study formula-feeding vs. natural rearing of lambs was used as a model to test the hypothesis that altered nutrition over this time would influence regional adipose tissue in the young adult at one year of age.
Methods: Singleton offspring from 16 twin-bearing ewes were randomly allocated to be reared with the ewe as a singleton (Control, n=8) or be separated from the ewe and solely receive formula (Formula-Fed, n=8) from birth to weaning (10-12 weeks). The quantity of formula allocated ad libitum (1-1.5 L/d Lamlac) was based upon current recommendations to maintain neonatal growth rates similar to ewe-reared offspring. After weaning all individuals were maintained together in an enclosed environment designed to promote increased growth rates and fat deposition to one year of age. Individuals were regularly weighed and blood samples taken during the fed and fasted state for determination of metabolic variables and at the end of experiments were humanely euthanased with electrocortical stunning and exsanguination. All animal protocols and procedures were ethically approved locally and performed under the UK Animals (Scientific Procedures) Act, 1986.
Results: Growth rate up to one year of age was greater in formula-fed relative to ewe-reared offspring with the result that these offspring were heavier at this time (maximum growth rate, 418±26 vs. 350±14 g/d P=0.002; weight at 1yr, 97±2 vs. 87±2 kg P=0.03; days to ½max weight 133±4.7 vs. 124±4 days P=NS, respectively). Total visceral adipose was similar between groups (7242±349 vs. 7791±429 g for control and formula-fed, respectively) but the regional deposition was different (e.g. % total deposited in omental and perirenal regions was 58±3 and 36±3 % respectively in Controls, but 48±2 and 47±2 % in formula-fed). Concentrations of circulating metabolites were unaltered in the fasted state (e.g. non-esterified fatty acids, 0.35±0.17 vs. 0.27±0.10 mmol/L; triglycerides 0.21±0.05 vs. 0.25±0.06 mmol/L, glucose 4.31±0.16 vs. 4.21±0.19 mmol/L in formula-fed and control sheep, respectively) but plasma homocysteine was elevated (18.8±1.7 vs. 12.2±0.4 μM).
Conclusions: In sheep, infant formula-feeding has no major effect on resting, fasted metabolic state but specifically results in an increase in plasma homocysteine concentration. Plasma homocysteine concentrations greater than 15 μM in humans predict increased risk of CVD. There was also a specific redistribution (10% shift) of internal adipose depots away from omental towards perirenal sites. The metabolic consequences of this shift are unclear but such an effect has not been seen in sheep to date, to our knowledge, following many diverse nutritional paradigms.