Leptin is involved in age-dependent changes in response to systemic inflammation in the rat
Leptin is involved in age-dependent changes in response to systemic inflammation in the rat
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DOI：
10.1016/j.bbi.2013.10.019
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发表时间：
2014-02-01
影响因子：
15.1
通讯作者：
Rummel, Christoph
中科院分区：
文献类型：
--
作者：
Koenig, Sandy;Luheshi, Giamal N.;Rummel, Christoph
肥胖导致亚临床外周和中枢炎症状态，通常与衰老有关。在这里，我们调查的来源和贡献的脂肪组织来源的细胞因子和瘦素样激素脂多糖（LPS）诱导的脑控制的疾病反应的年龄相关的变化。老年（24个月）和幼年（2个月）大鼠单独用LPS或盐水或与中和瘦素抗血清（LAS）或对照血清联合进行攻击。通过生物遥测监测疾病反应的变化。此外，用LPS或盐水刺激来自年轻和年老大鼠的离体脂肪外植体，收集培养基并通过精氨酸特异性生物测定/ELISA进行分析。我们发现增强的持续时间/程度的疾病症状，包括延迟，但长期发热老年大鼠。这种反应伴随着白细胞介素（IL）-6和IL-1 ra的血浆水平升高，以及通过RTPCR分析的脑和肝脏中炎症标志物的过度表达，包括抑制剂κ B α、微粒体前列腺素合酶和环氧合酶2（脑）。此外，我们第一次能够在LPS治疗的老年动物中显示长期升高的血浆瘦素水平。LAS治疗年轻大鼠倾向于减弱早期和老年大鼠的长期发热反应。脂肪外植体表现出不变的IL-6，但减少IL-1 ra和肿瘤坏死因子（TNE）-α释放的脂肪组织相比，年轻的动物。此外，我们发现老年动物中内源性免疫调节因子microRNA 146 a的表达增加，表明这些介质在对抗脑炎症中的作用。总的来说，我们的研究结果表明脂肪组织和瘦素在“衰老相关炎症”和年龄依赖性发热反应的修饰中的作用。(C)2013 Elsevier Inc. All rights reserved.
Obesity contributes to a state of subclinical peripheral and central inflammation and is often associated with aging. Here we investigated the source and contribution of adipose tissue derived cytokines and the cytokine-like hormone leptin to age-related changes in lipopolysaccharide (LPS)-induced brain-controlled sickness-responses. Old (24 months) and young (2 months) rats were challenged with LPS or saline alone or in combination with a neutralizing leptin antiserum (LAS) or control serum. Changes in the sickness-response were monitored by biotelemetry. Additionally, ex vivo fat-explants from young and old rats were stimulated with LPS or saline and culture medium collected and analyzed by cytokine-specific bioassays/ELISAs. We found enhanced duration/degree of the sickness-symptoms, including delayed but prolonged fever in old rats. This response was accompanied by increased plasma-levels of interleukin (IL)-6 and IL-1ra and exaggerated expression of inflammatory markers in brain and liver analyzed by RTPCR including inhibitor kappa B alpha, microsomal prostaglandin synthase and cyclooxygenase 2 (brain). Moreover, for the first time, we were able to show prolonged elevated plasma leptin-levels in LPS-treated old animals. Treatment with LAS in young rats tended to attenuate the early- and in old rats the prolonged febrile response. Fat-explants exhibited unchanged IL-6 but reduced IL-1ra and tumor necrosis factor (TNE)-alpha release from adipose tissue of aged compared to young animals. In addition, we found increased expression of the endogenous immune regulator microRNA146a in aged animals suggesting a role for these mediators in counteracting brain inflammation. Overall, our results indicate a role of adipose tissue and leptin in "aging-related-inflammation" and age-dependent modifications of febrile-responses. (C) 2013 Elsevier Inc. All rights reserved.