Effects of methotrexate on inflammatory alterations induced by obesity: An in vivo and in vitro study

被引:26
作者
DeOliveira, Caroline Candida [1 ]
Acedo, Simone Coghetto [1 ]
Ferreira Gotardo, Erica Martins [1 ]
Carvalho, Patricia de Oliveira [1 ]
Rocha, Thalita [1 ]
Pedrazzoli, Jose, Jr. [1 ]
Gambero, Alessandra [1 ]
机构
[1] Univ Sao Francisco, Sch Med, Clin Pharmacol & Gastroenterol Unit, BR-12916900 Braganca Paulista, SP, Brazil
基金
巴西圣保罗研究基金会;
关键词
Adipokines; Macrophages; iNOS; Adipose tissue; Adipocytes; JNK; NECROSIS-FACTOR-ALPHA; ADIPOSE-TISSUE; ADENOSINE A(2A); EXPRESSION; RECEPTOR; INTERLEUKIN-6; SUPPRESSION; MECHANISMS; DIET;
D O I
10.1016/j.mce.2012.03.016
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:92 / 98
页数:7
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