Effect of gender on long‐term effects of catch‐up growth in neonatal rats

Abstract

Poor early growth in preterm infants leads to impaired neurodevelopment but may reduce the risk of metabolic syndrome. Although elevated leptin levels in young animals may increase the risk of later leptin resistance, hepatic steatosis and metabolic syndrome, it is required for normal neurocognitive development. We therefore examined the effect of differences in early growth rates on serum leptin, triglycerides (TG) and cognition. Newborn rat pups were randomized into normal (N, n=10) or reduced growth (R, n=16) litters. On d11, R pups were re‐randomized into litters creating catch‐up (R‐6, n=6), normal (R‐10, n=10) or reduced growth (R‐16, n=10). Serum leptin, serum TG and hepatic TG were measured at d 10, 22, and 60; cognition in a T‐maze on d35. Leptin was higher in N pups than R on d10 (p<0.0001), and N animals scored highest on the T‐maze. In females, leptin on d22 and T‐maze score were significantly lower in the R‐16 group than other R groups. On d10, serum TG was significantly higher in N than R pups (p=0.001). In females, hepatic TG was significantly greater in R‐6 and N animals than in R‐10 or R‐16. We conclude that early growth restriction leads to lower serum leptin, serum TG, and impaired long‐term cognitive development. Subsequent catch‐up growth improves cognition, but worsens hepatic steatosis, in female rats. This model may contribute to our understanding of poor developmental outcomes in preterm infants.Grant Funding Source: UC Davis Department of Pediatrics