Endocrine Abstracts

Increases in proinflammatory pathways and macrophages in adipose tissue (AT) have been implicated in the metabolic complications of obesity (1). Nutrient-restriction (NR) in early to mid gestation reduces maternal plasma cortisol and increases fetal AT (2). Uncoupling protein (UCP)-2 is genetically linked to obesity and type 2 diabetes, and has been implicated in macrophage-mediated immunity. The effect of maternal NR in early to mid and late gestation on UCP2 and glucocorticoid receptor (GCR) mRNA abundance in ovine neonatal and adolescent AT has not been determined.

Twelve singleton-bearing ewes were either NR, receiving 60% of their energy requirements from 28 to 80 days gestation, or fed 100% requirements throughout pregnancy (Controls-C), and 14 twin-bearing ewes were fed either 60% (NR) or 100% (C) of their energy requirements from 110 days gestation up to term 147-days gestation, when they all gave birth spontaneously. Offspring were tissue sampled at 6 hours and 30 days after birth (twins) or at 6 months (singletons). mRNA abundance was measured by RT-PCR using oligonucleotide primers designed specifically to ovine UCP2 and GCR. Results are given as means (plus/minus SEM) relative to 18S rRNA.

AT weights were similar between groups and increased with postnatal age. UCP2 mRNA peaked at 6 hours, while GCR mRNA increased with age. Late NR decreased UCP2 mRNA [6 hours: C 81.1 (2.9), NR 54.8 (4.5), p<0.01; 30 days: C 41.8 (1.4), NR 32.4 (1.0), p<0.05], but increased GCR mRNA abundance [6 hours: C 81.5 (2.0), NR 96.7 (3.7), p<0.01; 30 days: C 82.8 (4.3), NR 129.2 (5.4), p<0.05]. This effect was reversed at 6 months by early to mid NR.

The timing of NR has differential effects on UCP2 and GCR mRNA abundance in AT. These effects may be important in promoting AT inflammation and subsequent fat mass development.

(1) Weisberg SP et al. The Journal of Clinical Investigation 112: 1796-1808 (2003).

(2) Bispham J et al. Endocrinology 144: 3575-3585 (2003).