Effects of early postnatal environment on hypothalamic gene expression in OLETF rats

<div><p>Previous reports have shown that the early postnatal environment has the ability to modify the obesity phenotype of Otsuka Long-Evans Tokushima Fatty (OLETF) rats. To determine whether this early postnatal environment affects hypothalamic signaling systems involved in energy balance, OLETF pups and lean Long-Evans Tokushima Otsuka (LETO) pups were cross-fostered to same or opposite strain Dams (designated as LdLp: LETO pups with LETO dams; LdOp: OLETF pups with LETO dams; OdLp: LETO pups with OLETF dams; and OdOp: OLETF pups with OLETF dams). Hypothalamic gene expression was examined at postnatal day 23 (PND 23) and PND 90 as OdOp rats started to gain more body weight at PND 23 and developed obesity at PND 90 relative to lean control LdLp rats. On PND 23, neuropeptide Y (<i>Npy</i>) gene expression was significantly increased in the dorsomedial hypothalamus (DMH) in both LdOp and OdOp pups compared to LdLp pups. Maternal environment did not affect DMH <i>Npy</i> expression in LETO weanlings. On PND 90, maternal environment during the cross-fostering period had a major effect on DMH <i>Npy</i> expression. Levels were significantly increased in both OdOp and OdLp rats relative to those in LdOp rats and LdLp controls. Reduced expression of <i>Npy</i> in the DMH of LdOp rats was consistent with their reduction of body weight compared to OdOp rats. In contrast to DMH <i>Npy</i>, gene expression for <i>Npy</i> and proopiomelanocortin in the arcuate nucleus appeared to appropriately respond to alterations in body weight and plasma leptin levels. Levels of oxytocin gene expression in the paraventricular nucleus were lower in offspring raised by LETO dams apparently responding to the higher DMH NPY levels. Together, our results demonstrate effects of both genotype and early postnatal environment on obesity of OLETF rats and further suggest an important role of DMH NPY in the development of obesity of OLETF rats.</p></div

Effects of genotype and maternal environment on ARC <i>Npy</i> and <i>Pomc</i> gene expression at PND 23 and PND 90.

<p>ARC <i>Npy</i> gene expression was not affected by either offspring genotype or maternal environment at PND 23 (A), but was significantly affected by offspring genotype at PND 90 (B). There were significant effects of both offspring genotype and maternal environment on ARC <i>Pomc</i> gene expression at both PND 23(C) and PND 90 (D). *p < .05 vs. LdLp, #p < .05 vs. LdOp and ^§p < .05 vs. OdLp.</p

In situ hybridization determinations of hypothalamic gene expression with ³⁵S-labeled antisense riboprobes.

<p>(A) <i>Npy</i> mRNA expression in the dorsomedial hypothalamus (DMH) and the arcuate nucleus (ARC); (B) <i>Pomc</i> mRNA expression in the ARC; (C) <i>Crf</i> mRNA expression in the paraventricular nucleus (PVN); (D) <i>Oxy</i> mRNA expression in the PVN and the supraoptic nucleus (SON).</p

Effect of maternal environment on body weight.

<p>(A) Mean body weights during the nursing period and (B) during the 90 day postnatal and post-weaning periods in the 4 groups of offspring (LdLp, LdOp, OdLp, and OdOp–designation of dam (d) and pup (p) genotypes [LETO (L) and OLETF (O) during the sucking period]). OLETF pups gained significantly more weight than did LETO pups. OLETF pups fostered to LETO dams gained less weight than OLETF pups that had been fostered to OLETF dams. Cross fostering had no effect on the weight gain of LETO pups.</p

Effects of genotype and maternal environment on PVN <i>Crf</i> and O<i>xt</i> gene expression at PND 23 and PND 90.

<p>There were no effects of offspring genotype or maternal environment on PVN <i>Cr</i>f gene expression at either time point (A and B). There was a significant effect of offspring genotype on PVN <i>Oxy</i> gene expression at PND 23 (C) and a significant effect of maternal environment on <i>Oxy</i> gene expression at PND 90 (D). *p < .05 vs. LdLp.</p