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

Abstract

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 (Npy) 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 Npy expression in LETO weanlings. On PND 90, maternal environment during the cross-fostering period had a major effect on DMH Npy expression. Levels were significantly increased in both OdOp and OdLp rats relative to those in LdOp rats and LdLp controls. Reduced expression of Npy in the DMH of LdOp rats was consistent with their reduction of body weight compared to OdOp rats. In contrast to DMH Npy, gene expression for Npy 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.

Social dominance predicts hippocampal glucocorticoid receptor recruitment and resilience to prenatal adversity

“…In parallel to the indirect inhibition enacted by hippocampal GR, the PVN itself possesses high levels of GR, which enacts direct inhibition of local CRF release 36 . While the early life environment has been shown to alter programming of hypothalamic gene expression 67 , we did not detect significant effects of either strain or restraint stress upon GR immunoreactivity in the PVN. These findings suggest that the wide-ranging roles of GR in the hypothalamus, including regulation of circadian rhythms and glucose metabolism, impart an evolutionary advantage to constant hypothalamic GR levels, regardless of behavioral phenotype or stress exposure.…”

Reduced Striatal Dopamine Transporter Availability and Heightened Response to Natural and Pharmacological Stimulation in CCK-1R-Deficient Obese Rats

“…Recent studies show that the mechanisms contributing to the obesity of OLETF rats are leptin-independent [67,[69][70][71] and involve hypothalamic NPY neurons [72]. We found no difference in corticosterone levels between the two strains (Figure 5).…”

“…Interestingly, this strain does not develop central or peripheral leptin resistance, suggesting that increases in serum leptin is likely a compensation to hyperphagia-induced obesity [68]. Recent studies show that the mechanisms contributing to the obesity of OLETF rats are leptin-independent [67,[69][70][71] and involve hypothalamic NPY neurons [72]. We found no difference in corticosterone levels between the two strains (Figure 5).…”

The role of oxytocin in regulation of appetitive behaviour, body weight and glucose homeostasis

“…Recently, levels of OXT gene expression in the PVN were measured on postnatal day 23 (PND 23) and PND 90 by in‐situ hybridisation in OLETF and LETO rats . PVN OXT expression was lower in OLETF rats both at PND 23 and PND 90 compared to lean LETO controls.…”