In man, low birth weight (BW) is associated with an increased risk of glucose intolerance in later life (Hales et al. 1991). In pigs, naturally induced low BW is also associated with poor glucose tolerance at 12 months of age, with no evidence of insulin deficiency (Poore & Fowden, 2000). The present study examined sensitivity to insulin, basal leptin concentrations and body fat depth in 3- and 12-month-old pigs of varying BW.
Experiments accorded with UK legislation. Forty-seven pure bred Large White pigs from 9 sows (15 litters) were used. Low (< 1.5 kg) and high (> 1.5 kg) BW piglets were selected from each litter. Piglets were weighed and measured at birth, ~3 months (m) and 12 m of age. At 3 and 12 m, selected pigs were tranquilised (azaperone alone (5 mg kg-1) or with ketamine (10 mg kg-1; at 3 m only); I.M.) and catheters were inserted into the dorsal aorta and vena cava via the femoral vessels under general anaesthesia (3-6 % halothane in O2 at 3 m; sodium pentobarbitone (20 mg kg-1; I.V.) at 12 m). At each age, insulin sensitivity was measured as the glucose decrement (mmol l-1 min-1) during the first 10 min after an insulin bolus (0.5 IU kg-1; I.V.) and as the glucose infusion rate (GIR) during a hyperinsulinaemic euglycaemic clamp (insulin infusion rates: 2 and 5 mU min-1 kg-1 at 12 and 3 m, respectively). Plasma glucose concentrations were measured enzymatically and insulin and leptin concentrations by RIA. Shoulder fat depth (SFD) was measured by ultrasound at 12 m only. Data (means ± S.E.M.) were analysed by Student’s t test and linear regression. Statistical significance is given by P ▓le│ 0.05.
Body weight of low BW pigs (23.5 ± 1.89 kg, n = 22) remained significantly smaller than high BW pigs (37.2 ± 2.52 kg, n = 25) at 3 m, but not at 12 m (low BW, 156.9 ± 8.4 kg, n = 10; high BW, 169.4 ± 6.0 kg, n = 8). Low BW pigs were significantly fatter than high BW pigs at 12 m (SFD: low BW, 38 ± 2 mm; high BW, 32 ± 1 mm). SFD was significantly negatively correlated to BW, body mass index (BMI) at birth, growth rate (GR; birth-3 m), but not to weight at 12 m. Plasma leptin levels at 12 m were significantly negatively correlated with SFD and positively associated with BW and BMI at birth in males only. At 3 m, leptin concentrations were significantly positively correlated to BW, BMI both at birth and 3 m but only in females. At 3 m, the glucose decrement was significantly positively associated with the head:abdominal circumference (AC) ratio at birth and the fractional GR (birth-1 m) in males but negatively associated with the head:AC ratio at 3 m in females. However, at 12 m the glucose decrement was significantly negatively correlated with fractional GR (0-1 m).
These studies show that low BW pigs catch up in body weight by gaining fat mass but this is associated with low plasma leptin concentrations in males, suggesting a possible disorder of adipose leptin expression or appetite regulation. Adult glucose intolerance in low BW pigs appears to be associated with low sensitivity to insulin at 12 m of age.