| Intrauterine growth restriction (IUGR) creates altered programming in many organs, including the hypothalamus. Programming involves adaptive changes initiated to protect the survival of a fetus following IUGR, which can adversely influence the later response of genes that regulating energy balance. In male mice, IUGR coupled with rapid postnatal catch-up growth predisposes towards early onset obesity. One potential mechanism for this obesity is altered hypothalamic programming of intrahypothalamic cues involving prepro-orexin and prepro-MCH, two energy balance regulating genes as well as the extra-hypothalamic cues of peripheral hormones leptin and insulin. We therefore hypothesized that IUGR would alter hypothalamic programming of prepro-orexin and prepro-MCH genes in association with altered serum leptin and insulin levels in male mice at postnatal day 7 (P7) and P60.;IUGR was induced via maternal thromboxane A2-analog infusion in the last week of C57BL/6J mouse gestation. Sham operated dams acted as controls. Sham and IUGR offspring were cross-fostered to unmanipulated dams and weaned to standard mouse chow at P21. In this mouse model, IUGR males, as compared to IUGR females, achieve rapid catch-up growth to sham males by P28 whereas IUGR females do not catch-up to sham females until P77. We measured mRNA levels via quantitative real-time RT-PCR, protein levels via Western immunoblotting, serum leptin and insulin levels via ELISA, and food intake from P21 to P60.;IUGR increased hypothalamic prepro-orexin protein levels and decreased MCH mRNA levels in P7 IUGR males. In conclusion, our findings of IUGR-induced altered hypothalamic programming of prepro-orexin and prepro-MCH are gender-specific and do not persist in the neonatal period, but into adulthood. Altered programming of genes such as prepro-orexin and prepro-MCH in the neonatal period may contribute to the differential catch-up growth observed between IUGR male and female mice in this model. |
