Neuropeptide Y and peptide YY protect from weight loss caused by Bacille Calmette-Guérin in mice.

Neuropeptide Y and peptide YY protect from weight loss caused by Bacille Calmette-Guérin in mice.
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DOI:
10.1111/bph.12354
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发表时间:
2013-11
影响因子:
7.3
通讯作者:
Holzer P
Holzer P
中科院分区:
医学2区
文献类型:
--
作者:
Painsipp E;Köfer MJ;Farzi A;Dischinger US;Sinner F;Herzog H;Holzer P

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据报道,用卡介苗(BCG)对小鼠进行免疫攻击会导致短暂的体重减轻和行为病反应。虽然卡介苗引起的抑郁症涉及犬尿氨酸途径,但体重减轻的发生与该因素无关。由于神经肽 Y (NPY) 和肽 YY (PYY) 参与食物摄入的调节,我们假设它们在 BCG 诱导的体重减轻中发挥作用。雄性野生型、PYY 敲除 (PYY−/−)、NPY 敲除 (NPY−/−) 和 NPY−/−;PYY−/− 双敲除小鼠注射载体或 BCG(每只小鼠约 108 个集落形成单位),并在治疗后 2 周记录它们的体重、运动、探查和摄食。 PYY 和 NPY 的缺失加剧了 BCG 诱导的体重损失,这在 NPY−/−;PYY−/− 小鼠中最为明显(最大损失:15%)。 NPY−/−;PYY−/− 小鼠的体重减轻在两周的观察期内并未恢复正常。卡介苗抑制了运动、探索和食物摄入的昼夜节律模式。然而,这些变化的时间进程与 BCG 在 NPY−/−;PYY−/− 小鼠中引起的长期体重减轻不同。 BCG 增加循环 IL-6 的作用(治疗后 16 天测量)并未因 PYY、NPY 或 NPY 加 PYY 的敲除而改变。这些数据表明,NPY 和 PYY 都需要防止 BCG 诱发的免疫挑战导致长期体重减轻和扰乱能量平衡。研究结果证明 NPY 和 PYY 在协调感染和免疫刺激的稳态反应中发挥着重要作用。
Immune challenge of mice with Bacille Calmette–Guérin (BCG) has been reported to cause transient weight loss and a behavioural sickness response. Although BCG-induced depression involves the kynurenine pathway, weight loss occurs independently of this factor. Because neuropeptide Y (NPY) and peptide YY (PYY) are involved in the regulation of food intake, we hypothesized that they play a role in the BCG-induced weight loss. Male wild-type, PYY knockout (PYY−/−), NPY knockout (NPY−/−) and NPY−/−;PYY−/− double knockout mice were injected with vehicle or BCG (approximately 108 colony-forming units per mouse), and their weight, locomotion, exploration and ingestion were recorded for 2 weeks post-treatment. Deletion of PYY and NPY aggravated the BCG-induced loss of body weight, which was most pronounced in NPY−/−;PYY−/− mice (maximum loss: 15%). The weight loss in NPY−/−;PYY−/− mice did not normalize during the 2 week observation period. BCG suppressed the circadian pattern of locomotion, exploration and food intake. However, these changes took a different time course than the prolonged weight loss caused by BCG in NPY−/−;PYY−/− mice. The effect of BCG to increase circulating IL-6 (measured 16 days post-treatment) remained unaltered by knockout of PYY, NPY or NPY plus PYY. These data show that NPY and PYY are both required to protect from the action of BCG-evoked immune challenge to cause prolonged weight loss and disturb energy balance. The findings attest to an important role of NPY and PYY in orchestrating homeostatic reactions to infection and immune stimulation.
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