The peroxisome proliferator activated receptor gamma (PPARγ) ligand rosiglitazone modulates bronchoalveolar lavage levels of leptin, adiponectin, and inflammatory cytokines in lean and obese mice
The peroxisome proliferator activated receptor gamma (PPARγ) ligand rosiglitazone modulates bronchoalveolar lavage levels of leptin, adiponectin, and inflammatory cytokines in lean and obese mice
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DOI：
10.1007/s00408-007-9035-9
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发表时间：
2007-12-01
期刊：
影响因子：
5
通讯作者：
Hart, C. Michael
中科院分区：
文献类型：
--
作者：
Holguin, Fernando;Rojas, Mauricio;Hart, C. Michael
缺乏瘦素受体 (db(-)/db(-)) 的肥胖小鼠已被证明具有先天支气管高反应性 (BHR)。有人提出，肥胖介导的 BHR 可能涉及瘦素增加和全身脂联素水平降低的组合。本研究的目的是确定肥胖是否会改变气道瘦素和脂联素浓度，以及使用合成的过氧化物酶体增殖物激活受体γ（PPARγ）配体治疗是否可以减少气道瘦素并增加气道脂联素。在这项研究中，肥胖、瘦素受体缺陷（db（-）/db-）或瘦（db（+）/db（-））小鼠每天接受罗格列酮（3 mg/kg/天）或载体灌胃治疗，持续 1 周。随后进行支气管肺泡灌洗（BAL）以确定瘦素、脂联素和炎症细胞因子的水平。罗格列酮治疗可增加瘦小鼠的 BAL 脂联素水平（p = 0.04），而肥胖小鼠的 BAL 脂联素水平则有所增加（p = 0.07）。罗格列酮治疗降低了瘦小鼠的瘦素水平，但增加了肥胖小鼠的支气管肺泡灌洗液中的瘦素水平（p < 0.01）。与肥胖载体治疗组相比，瘦型罗格列酮治疗组中粒细胞-巨噬细胞集落刺激因子（GM-CSF）的BAL水平较低，并且与肥胖载体治疗组相比，肥胖罗格列酮治疗组中粒细胞-巨噬细胞集落刺激因子（GM-CSF）的BAL水平较低。这些结果表明，肥胖与气道中脂肪因子和细胞因子水平的改变有关，这些改变可以通过罗格列酮治疗来调节。
Obese mice that lack leptin receptor (db(-)/db(-)) have been shown to have innate bronchial hyperresponsiveness (BHR). It has been proposed that the obesity-mediated BHR may involve a combination of increased leptin and reduced systemic adiponectin levels. The aim of this study was to determine if obesity modifies the airway concentration of leptin and adiponectin and whether treatment with a synthetic peroxisome proliferator-activated receptor gamma (PPAR gamma) ligand can reduce airway leptin and increase airway adiponectin. In this study, obese, leptin receptor-deficient (db(-)/db-), or lean (db(+)/db(-)) mice were treated with rosiglitazone (3 mg/kg/day) or vehicle by gavage daily for 1 week. Bronchioalveolar lavage (BAL) was subsequently performed to determine levels of leptin, adiponectin, and inflammatory cytokines. Treatment with rosiglitazone increased BAL adiponectin levels in lean (p = 0.04) and to a lesser extent in obese mice (p = 0.07). Rosiglitazone treatment lowered leptin levels in lean mice, but increased leptin levels in BAL fluid of obese mice (p < 0.01). The BAL levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) were lower in the lean rosiglitazone-treated group compared with the obese vehicle-treated group and lower in the obese rosiglitazone-treated group compared with the obese vehicle-treated group. These results demonstrate that obesity is associated with alterations in adipokine and cytokine levels in the airways that can be modulated by treatment with roziglitazone.