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Background: There is increasing evidence that poor growth of preterm infants is a risk factor for poor long-term development, while the effects of early postnatal growth restriction are not well known. We utilized a rat model to examine the consequences of different patterns of postnatal growth and hypothesized that early growth failure leads to impaired development and insulin resistance. Rat pups were separated at birth into normal (N, n = 10) or restricted intake (R, n = 16) litters. At d11, R pups were re-randomized into litters of 6 (R-6), 10 (R-10) or 16 (R-16) pups/dam. N pups remained in litters of 10 pups/dam (N-10). Memory and learning were examined through T-maze test. Insulin sensitivity was measured by i.p. insulin tolerance test and glucose tolerance test. Results: By d10, N pups weighed 20 % more than R pups (p < 0.001). By d15, the R-6 group caught up to the N-10 group in weight, the R-10 group showed partial catch-up growth and the R-16 group showed no catch-up growth. All R groups showed poorer scores in developmental testing when compared with the N-10 group during T-Maze test (p < 0.05). Although R-16 were more insulin sensitive than R-6 and R-10, all R groups were more glucose tolerant than N-10. Conclusion: In rats, differences in postnatal growth restriction leads to changes in development and in insulin sensitivity. These results may contribute to better elucidating the causes of poor developmental outcomes in human preterm infants.

The Wnt/beta-catenin/TCF4 pathway plays critical roles in the maintenance of small intestinal epithelium; however, downstream targets of the beta-catenin/TCF4 complex are not extensively characterized. We identified miR-30e as an immediate target activated by the beta-catenin/TCF4 complex. miR-30e was detected in the peri-nuclear region of the intestinal crypt IEC-6 cells. Bioinformatics analysis revealed clustered beta-catenin/TCF4 binding sites within the miR-30e promoter region. This promoter region was cloned into pGL3-control luciferase reporter vector, with the enhancer region removed. Transfection of pCMV-SPORT6-beta-catenin expression vector dose-dependently increased luciferase activity, and co-transfection of pCMV-SPORT6-TCF4 expression vector further enhanced the promoter activity. Dexamethasone-induced IEC-6 cells differentiation caused a 2.5-fold increase in miR-30e expression, and upon beta-catenin siRNA transfection, miR-30e increased 1.3-fold. Electrophoretic mobility shift assay and chromatin immunoprecipitation assay confirmed the binding between beta-catenin/TCF4 complexes from IEC-6 nuclear extracts and the putative sequences in the miR-30e promoter. These results demonstrate that beta-catenin/TCF4 transactivates miR-30e during intestinal cell differentiation.

BackgroundLeptin, the product of the obese (ob) gene, is a regulator of food intake and energy metabolism. Immunoreactive leptin was detected recently in breast milk and it has been hypothesized that leptin may be absorbed and may contribute to differences in body composition between breast-fed and formula-fed infants.ObjectiveThe objective was to evaluate whether diet, adiposity, or sex affect plasma leptin in breast-fed and formula-fed infants.DesignVenous blood samples were drawn from healthy, exclusively breast-fed or formula-fed Swedish infants at 1, 4, and 6 mo of age (n = 193) and from 12-mo-old Finnish infants (n = 79). Anthropometric measurements were made and plasma samples were analyzed for leptin, insulin, and glucose.ResultsThere were no significant differences in plasma leptin between formula-fed and breast-fed infants at 1 and 4 mo of age, whereas formula-fed infants had significantly higher ( approximately 5%) leptin concentrations at 6 mo of age. Similar results were observed after correction for BMI. Plasma leptin was 15-25% higher in female than in male infants at 1, 4, and 12 mo of age (P < 0.05), also after correction for BMI. When all infants were analyzed together, a positive correlation (r = 0.34, P < 0.0001) was found between plasma leptin and BMI. Very low leptin concentrations were found in breast milk after centrifugation and the high concentrations reported previously were likely due to interference in the assay by milk fat.ConclusionsPlasma leptin concentrations are not higher in breast-fed than in formula-fed infants; however, sex and adiposity affect leptin concentrations even at this early age.