Iwasa Takeshi, Matsuzaki Toshiya, Kinouchi Riyo, Fujisawa Shinobu, Murakami Masahiro, Kiyokawa Machiko, Kuwahara Akira, Yasui Toshiyuki, Irahara Minoru
Department of Obstetrics and Gynecology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan.
Int J Dev Neurosci. 2010 Feb;28(1):119-24. doi: 10.1016/j.ijdevneu.2009.08.015. Epub 2009 Sep 4.
It has been reported that prenatal immune stress induced by lipopolysaccharides or cytokines increases food intake and leads to obesity and other features of metabolic syndrome in adulthood. Using Sprague-Dawley rats, we evaluated whether neonatal LPS injection altered their body weight regulation systems under non-stress and immune stress conditions. On Day 10 after birth, all pups were injected with LPS (100 microg/kg, i.p.) (PND(10)LPS) or saline (PND(10)Saline). After weaning, body weight was significantly elevated in PND(10)LPS compared with PND(10)Saline. Thereafter, the rats were injected with LPS (100 microg/kg, i.p.) or saline (used as a basal condition) from 7 to 8 weeks of age. Under basal conditions, cumulative food intake were significantly higher, serum leptin concentration was significantly increased, and hypothalamic NPY mRNA expression was significantly decreased in PND(10)LPS compared with PND(10)Saline. Under adult LPS injected conditions, body weight gain and cumulative food intake were suppressed in both the PND(10)LPS and PND(10)Saline groups compared with those observed under basal adult saline-injected conditions. The suppressive effects induced by adult LPS injection were less evident in the PND(10)LPS group than in the PND(10)Saline group. Adult LPS injection increased the serum leptin concentration in the PND(10)Saline rats, but not in the PND(10)LPS rats. In addition, adult LPS injection increased the mRNA expression of anorexinergic factors (IL-1beta, and TNF-alpha), and decreased that of the orexinergic factor NPY in both groups. However, the influence of adult LPS injection upon these factors was less evident in the PND(10)LPS group than in the PND(10)Saline group. These results suggest that neonatal LPS injection alters body weight regulation under both non-stress and immune stress conditions in male rats. Changes in the endocrine, neuropeptide, and cytokine regulation systems might be involved in these alterations.
据报道，脂多糖或细胞因子诱导的产前免疫应激会增加食物摄入量，并导致成年期肥胖和代谢综合征的其他特征。我们使用Sprague-Dawley大鼠，评估新生期注射脂多糖是否会在非应激和免疫应激条件下改变其体重调节系统。出生后第10天，所有幼崽均腹腔注射脂多糖（100微克/千克）（出生后第10天脂多糖组）或生理盐水（出生后第10天生理盐水组）。断奶后，与出生后第10天生理盐水组相比，出生后第10天脂多糖组的体重显著升高。此后，在7至8周龄时，给大鼠注射脂多糖（100微克/千克，腹腔注射）或生理盐水（作为基础条件）。在基础条件下，与出生后第10天生理盐水组相比，出生后第10天脂多糖组的累积食物摄入量显著更高，血清瘦素浓度显著升高，下丘脑神经肽Y（NPY）mRNA表达显著降低。在成年期注射脂多糖的条件下，与基础成年期注射生理盐水条件下观察到的情况相比，出生后第10天脂多糖组和出生后第10天生理盐水组的体重增加和累积食物摄入量均受到抑制。成年期注射脂多糖诱导的抑制作用在出生后第10天脂多糖组中比在出生后第10天生理盐水组中不太明显。成年期注射脂多糖使出生后第10天生理盐水组大鼠的血清瘦素浓度升高，但未使出生后第10天脂多糖组大鼠的血清瘦素浓度升高。此外，成年期注射脂多糖使两组中厌食性因子（白细胞介素-1β和肿瘤坏死因子-α）的mRNA表达增加，使食欲性因子神经肽Y的mRNA表达降低。然而，成年期注射脂多糖对这些因子的影响在出生后第10天脂多糖组中比在出生后第10天生理盐水组中不太明显。这些结果表明，新生期注射脂多糖会在雄性大鼠的非应激和免疫应激条件下改变体重调节。内分泌、神经肽和细胞因子调节系统的变化可能与这些改变有关。
