Birth size and early postnatal growth influence the risk of adverse adult health such as obesity and metabolic disorders. Previously, we have shown that postnatal undernutrition (UN) improves glucose tolerance, while combined pre- and postnatal UN increases fatness, in young adult (1.5 year-old) female sheep (Poore et al., 2003, 2004). In the current study, the interaction between poor development in early gestation and adverse postnatal conditions on adiposity and metabolism has been examined in mature adult sheep. Ewes received either 100% (group C, n = 39) or 50% of global nutritional requirements (group U, n = 41) from conception—day 30 gestation, and 100% thereafter (Animals (Scientific Procedures) Act 1986). Offspring were fed ad lib. (CC, n = 22; UC, n = 19) or to reduce body weight to 85% of target (predicted from 0—12 weeks growth trajectory) from 12—25 weeks postnatal age and ad lib. thereafter (CU, n = 17; UU, n = 22). At age 2.5 years, body condition score (BCS) was assessed and fat depth measured by ultrasound then corrected for body weight. Arterial and venous catheters were inserted under general anaesthesia (3% halothane/O2). Glucose handling was determined by areas (AUC) under the glucose and insulin curves following i.v. glucose (0.5 g/kg). Plasma insulin was measured by ELISA. Data were analysed by linear regression (population) and ANOVA (4 groups). In all female, but not male, adult sheep, glucose tolerance at 2.5 years worsened (increased glucose AUC) with increasing BCS (r2 = 0.26, p < 0.005). However, glucose AUC was reduced (p < 0.05) by postnatal UN in 2.5 year-old females, not males, regardless of previous prenatal nutrition (CU and UU). The increased fat depth in 1.5 year-old UU females was no longer evident at 2.5 years, although fat depth at this age was related to 12—25 week growth (r2 = —0.10, p = 0.05) and fatness at 1.5 years (r2 = 0.19, p < 0.05). Pre- or postnatal UN had no effect on insulin AUC at 2.5 years in either sex. These findings show that the association between relatively poor glucose tolerance and higher body condition in female sheep is disrupted by early postnatal UN. The improvement in glucose handling in female sheep who faced UN in early postnatal life persists until 2.5 years of age and is likely due to an increase in insulin sensitivity rather than secretion. Improved glucose utilisation may aid subsequent recovery of body weight, although it is unclear whether this strategy would be beneficial in the longer term.
King's College London (2005) J Physiol 565P, C155
Communications: Glucose metabolism and body composition in mature adult sheep following early life undernutrition
Poore, Kirsten R; Cleal, Jane K; Newman, Jim P; Boullin, Julian ; Noakes, David ; Hanson, Mark A; Green, Lucy R;
1. Centre for Developmental Origins of Health and Disease, University of Southampton, Southampton, United Kingdom. 2. Department of Veterinary Reproduction, Royal Veterinary College, North Mymms, United Kingdom.
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