Role of A1 and A2A adenosine receptor agonists in adipose tissue inflammation induced by obesity in mice
Role of A1 and A2A adenosine receptor agonists in adipose tissue inflammation induced by obesity in mice
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DOI：
10.1016/j.ejphar.2017.02.017
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发表时间：
2017-03-15
影响因子：
5
通讯作者：
Gambero, Alessandra
中科院分区：
文献类型：
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作者：
DeOliveira, Caroline Candida;Caria, Cintia Rabelo E. Paiva;Gambero, Alessandra
腺苷受体在脂肪组织中表达，并控制生理和病理事件，如脂解和炎症。本研究的目的是评价N-6-环戊基腺苷（CPA）的活性，CPA是一种有效的和选择性的A（1）腺苷受体激动剂; 2-p-（2-羧乙基）苯乙氨基-5 '-N-乙酰胺腺苷盐酸盐（CGS-21680），一种A（2A）腺苷受体激动剂;和5 '-N-乙基羧酰胺腺苷（NECA），一种有效的非选择性腺苷受体激动剂，对小鼠肥胖诱导的脂肪组织炎症改变的影响。瑞士小鼠喂食高脂肪饮食12周，最后两周给予激动剂。评价体重、肥胖和血糖稳态。通过评价脂肪因子产生和巨噬细胞浸润来评估脂肪组织中的炎症。还评价了脂肪组织中的腺苷受体信号传导。接受CGS 21680的小鼠表现出与全身性降低的炎症标志物（TNF-α、PAI-1）和内脏脂肪组织（INF-α、MCP-1、巨噬细胞浸润）相关的葡萄糖稳态的改善。在该组小鼠的脂肪组织中发现p38信号传导的激活。NECA治疗的小鼠表现出与观察到的体重减轻相关的葡萄糖稳态的一些改善。接受CPA的小鼠仅表现出在内脏脂肪组织内测量的离体基础脂解率的降低。总之，A2 A受体激动剂对肥胖小鼠的给药导致葡萄糖稳态和脂肪组织炎症的改善，证实了治疗肥胖的新疗法可以从这些化合物中出现的想法。
Adenosine receptors are expressed in adipose tissue and control physiological and pathological events such as lipolysis and inflammation. The aim of this study was to evaluate the activity of N-6-cyclopentyladenosine (CPA), a potent and selective A(1) adenosine receptor agonist; 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarbox-yamidoadenosine hydrochloride (CGS-21680), an A(2A) adenosine receptor agonist; and 5'-N-ethylcarboxami-doadenosine (NECA), a potent non-selective adenosine receptor agonist on adipose tissue inflammatory alterations induced by obesity in mice. Swiss mice were fed with a high-fat diet for 12 weeks and agonists were administered in the last two weeks. Body weight, adiposity and glucose homeostasis were evaluated. Inflammation in adipose tissue was assessed by evaluation of adipokine production and macrophage infiltration. Adenosine receptor signaling in adipose tissue was also evaluated. Mice that received CGS21680 presented an improvement in glucose homeostasis in association with systemically reduced inflammatory markers (TNF-alpha, PAI-1) and in the visceral adipose tissue (INF-alpha, MCP-1, macrophage infiltration). Activation of p38 signaling was found in adipose tissue of this group of mice. NECA-treated mice presented some improvements in glucose homeostasis associated with an observed weight loss. Mice that received CPA presented only a reduction in the ex vivo basal lipolysis rate measured within visceral adipose tissue. In conclusion, administration of the A2A receptor agonist to obese mice resulted in improvements in glucose homeostasis and adipose tissue inflammation, corroborating the idea that new therapeutics to treat obesity could emerge from these compounds.