Effects of methotrexate on inflammatory alterations induced by obesity: An in vivo and in vitro study
Effects of methotrexate on inflammatory alterations induced by obesity: An in vivo and in vitro study
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DOI：
10.1016/j.mce.2012.03.016
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发表时间：
2012-09-25
影响因子：
4.1
通讯作者：
Gambero, Alessandra
中科院分区：
文献类型：
--
作者：
DeOliveira, Caroline Candida;Acedo, Simone Coghetto;Gambero, Alessandra
免疫抑制药物，如甲氨蝶呤，能够抑制细胞因子的产生和白细胞迁移到炎症灶;因此，它们可以改变肥胖期间脂肪组织中炎症的建立。因此，我们研究了甲氨蝶呤在体内对高脂饮食诱导的小鼠肥胖的影响，以及在体外对分离和共培养的脂肪细胞和巨噬细胞的影响。用甲氨蝶呤治疗的肥胖小鼠呈现出降低的血清TNF-α、胰岛素和葡萄糖水平，以及胰岛素敏感性的改善。这些小鼠的脂肪组织产生较少的促炎因子（TNF-α，IL-6，瘦素）和更多的抗炎脂肪因子（脂联素和IL-10），与减少的巨噬细胞浸润和炎症相关。在分离和共培养的脂肪细胞和巨噬细胞中也证实了细胞因子抑制。甲氨蝶呤在体内和体外通过腺苷释放产生抗脂解作用。结合联合收割机抗脂肪分解作用和控制脂肪组织炎症的能力的药物可以在控制胰岛素抵抗和与肥胖相关的其他病理中发挥作用。(c)2012爱思唯尔爱尔兰有限公司保留所有权利。
Immunosuppressant drugs, such as methotrexate, are able to inhibit cytokine production and leukocyte migration to inflammatory foci; therefore, they could modify the establishment of inflammation in adipose tissue during obesity. Thus, we studied the effects of methotrexate in vivo on high-fat diet induced-obesity in mice and in vitro in isolated and co-cultured adipocytes and macrophages. Obese mice treated with methotrexate presented reduced serum levels of TNF-alpha, insulin and glucose, and an improvement of insulin sensitivity. Adipose tissue from these mice produced less proinflammatory (TNF-alpha, IL-6, leptin) and more anti-inflammatory adipokines (adiponectin and IL-10) associated with reduced macrophage infiltration and inflammation. Cytokine inhibition was also confirmed in isolated and co-cultured adipocytes and macrophages. Methotrexate presented anti-lipolytic effect in vivo and, in vitro through adenosine release. Drugs that combine anti-lipolytic effect and the ability to control inflammation in adipose tissue could play a role in the control of insulin resistance and other pathologies associated with obesity. (c) 2012 Elsevier Ireland Ltd. All rights reserved.