Lipopolysaccharide (LPS) stimulates adipokine and socs3 gene expression in mouse brain and pituitary gland in vivo, and in N-1 hypothalamic neurons in vitro
Lipopolysaccharide (LPS) stimulates adipokine and socs3 gene expression in mouse brain and pituitary gland in vivo, and in N-1 hypothalamic neurons in vitro
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DOI：
10.1016/j.jneuroim.2009.02.001
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发表时间：
2009-04-30
影响因子：
3.3
通讯作者：
Wilkinson, Michael
中科院分区：
文献类型：
--
作者：
Brown, Russell;Imran, Syed A.;Wilkinson, Michael
调节代谢和炎症反应的脂肪因子，如rfmin和禁食诱导的脂肪因子，也在小鼠脑和垂体中表达。由于脂多糖（LPS）诱导的内毒素血症通过下丘脑依赖性机制引起厌食反应，我们假设LPS也会改变下丘脑脂肪因子的表达。用LPS（5mg/kg; s.c.）体重显著降低（24 h），实时RT-PCR显示下丘脑、垂体、皮质和脂肪组织中的rfA、fAF和细胞因子信号传导抑制因子-3（socs-3）mRNA的时间和组织依赖性增加。下丘脑和垂体中的基因表达迅速增加（3-6 h），但在24 h内恢复正常。相比之下，在注射后24小时，除脂肪中的rfos外，靶基因的表达在皮质和内脏脂肪中保持升高。为了更具体地研究下丘脑对LPS的反应，我们在体外直接研究了其对N-1下丘脑神经元的作用。LPS（25 μ g/mL; 3 h）对rfA 1 mRNA无影响，但显著刺激fAF和socs-3表达。虽然各种Toll样受体4（TLR 4）拮抗剂（parthenocyte、PD 098059和SB 202190）不能阻止LPS诱导的fiaf和socs-3的增加，但它们确实部分减弱了其刺激作用。我们的结论是，LPS治疗增加了中央，可能是神经元，脂肪因子基因的表达，这可能会影响局部组织修复和功能，但也可能有下游的后果下丘脑控制的食欲和能量代谢后的炎症损伤。(C)2009 Elsevier B. V.保留所有权利。
Adipokines that modulate metabolic and inflammatory responses, such as resistin (rstn) and fasting-induced adipose factor (fiaf), are also expressed in mouse brain and pituitary gland. Since lipopolysaccharide (LPS)induced endotoxinemia provokes an anorectic response via a hypothalamic-dependent mechanism we hypothesized that LPS would also modify hypothalamic adipokine expression. Challenging male CD-1 mice with LPS (5 mg/kg; s.c.) significantly reduced bodyweight (24 h) and realtime RT-PCR revealed time- and tissue-dependent increases in rstn, fiaf and suppressor of cytokine signaling-3 (socs-3) mRNA in hypothalamic, pituitary, cortical and adipose tissues. Gene expression was rapidly increased (3-6 h) in the hypothalamus and pituitary, but returned to normal within 24 h. In contrast, with the exception of rstn in fat, the expression of target genes remained elevated in cortex and visceral fat at 24 h post-injection. In order to more specifically examine the hypothalamic response to LPS we investigated its effects directly on N-1 hypothalamic neurons in vitro. LPS (25 mu g/mL; 3 h) had no effect on rstn mRNA, but significantly stimulated fiaf and socs-3 expression. Although various toll-like receptor 4 (TLR4) antagonists (parthenolide, PD098059, and SB202190) did not prevent the LPS-induced increases in fiaf and socs-3, they did partially attenuate its stimulatory effects. We conclude that LPS treatment increases the expression of central, and possibly neuronal, adipokine genes which may influence local tissue repair and function, but could also have downstream consequences on the hypothalamic control of appetite and energy metabolism following an inflammatory insult. (C) 2009 Elsevier B.V. All rights reserved.