Kim Yonwook J, Schroeder Mariana, Liang Nu-Chu, Moran Timothy H, Weller Aron, Bi Sheng
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
Psychology Department and Gonda Brain Research Center, Bar Ilan University, Ramat-Gan, Israel.
PLoS One. 2017 Jun 2;12(6):e0178428. doi: 10.1371/journal.pone.0178428. eCollection 2017.
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.
先前的报告表明，出生后的早期环境有能力改变大冢长崎德岛肥胖（OLETF）大鼠的肥胖表型。为了确定这种出生后的早期环境是否会影响参与能量平衡的下丘脑信号系统，将OLETF幼崽和瘦型长崎德岛大冢（LETO）幼崽交叉寄养给同品系或异品系的母鼠（分别指定为LdLp：LETO幼崽由LETO母鼠抚养；LdOp：OLETF幼崽由LETO母鼠抚养；OdLp：LETO幼崽由OLETF母鼠抚养；OdOp：OLETF幼崽由OLETF母鼠抚养）。在出生后第23天（PND 23）和第90天（PND 90）检测下丘脑基因表达，因为相对于瘦型对照LdLp大鼠，OdOp大鼠在PND 23开始体重增加更多，并在PND 90发展为肥胖。在PND 23时，与LdLp幼崽相比，LdOp和OdOp幼崽的背内侧下丘脑（DMH）中神经肽Y（Npy）基因表达显著增加。母鼠环境对LETO断奶幼崽的DMH Npy表达没有影响。在PND 90时，交叉寄养期间的母鼠环境对DMH Npy表达有重大影响。相对于LdOp大鼠和LdLp对照，OdOp和OdLp大鼠中的水平显著增加。与OdOp大鼠相比，LdOp大鼠DMH中Npy表达降低与其体重减轻一致。与DMH Npy相反，弓状核中Npy和阿黑皮素原的基因表达似乎能适当响应体重和血浆瘦素水平的变化。由LETO母鼠抚养的后代室旁核中催产素基因表达水平较低，这显然是对较高的DMH NPY水平的反应。总之，我们的结果证明了基因型和出生后早期环境对OLETF大鼠肥胖的影响，并进一步表明DMH NPY在OLETF大鼠肥胖发展中的重要作用。
