Pioglitazone improves lipid and insulin levels in overweight rats on a high cholesterol and fructose diet by decreasing hepatic inflammation
Pioglitazone improves lipid and insulin levels in overweight rats on a high cholesterol and fructose diet by decreasing hepatic inflammation
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DOI：
10.1111/j.1476-5381.2010.00671.x
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发表时间：
2010-08-01
影响因子：
7.3
通讯作者：
Fantozzi, Roberto
中科院分区：
文献类型：
--
作者：
Collino, Massimo;Aragno, Manuela;Fantozzi, Roberto
背景与目的：营养过剩导致肥胖和胰岛素抵抗。吡格列酮是一种选择性过氧化物酶体增殖物激活受体（PPAR）γ激动剂，目前用于治疗胰岛素抵抗，但其激活的具体分子机制尚未完全了解。最近的研究表明，细胞因子信号转导抑制因子（SOCS）-3参与胰岛素抵抗的发病机制。本研究旨在探讨肝脏信号通路激活的过氧化物酶体增殖物激活受体γ激活在非遗传性胰岛素抵抗动物model.Experimental方法：雄性Wistar大鼠维持高胆固醇果糖（HCF）饮食15周。在该饮食的最后4周，经口给予吡格列酮（3 mg中心点kg-1）。在处理结束时，收集血清用于生化分析。在大鼠肝脏中评估了PPAR γ、SOCS-3、促炎标志物、胰岛素受体底物-2和Akt/糖原合成酶激酶-3 β磷酸化的水平。关键结果：喂食HCF饮食的大鼠表现出高脂血症、高胰岛素血症、葡萄糖耐量受损和胰岛素抵抗。吡格列酮给药引起脂质代谢和胰岛素反应性的显着改善。这伴随着SOCS-3、白细胞介素-6、肿瘤坏死因子-α和中性粒细胞浸润标志物的肝脏表达减少。饮食诱导的过氧化物酶体增殖物激活受体γ的表达是不受影响的吡格列酮treatment.Conclusion和影响：慢性吡格列酮给药减少大鼠喂HCF饮食的肝脏炎症反应。这些作用与SOCS-3的肝脏表达的变化有关，这可能是减少局部炎症和改善胰岛素信号传导之间的关键联系。1889年至1891年，在此期间。要查看此评论，请访问http://dx.doi.org/10.1111/j.1476-5381.2010.00739.x。
Background and purpose:Nutrient overload leads to obesity and insulin resistance. Pioglitazone, a selective peroxisome proliferator-activated receptor (PPAR)gamma agonist, is currently used to manage insulin resistance, but the specific molecular mechanisms activated by PPAR gamma are not yet fully understood. Recent studies suggest the involvement of suppressor of cytokine signalling (SOCS)-3 in the pathogenesis of insulin resistance. This study aimed to investigate the hepatic signalling pathway activated by PPAR gamma activation in a non-genetic insulin-resistant animal model.Experimental approach:Male Wistar rats were maintained on a high-cholesterol fructose (HCF) diet for 15 weeks. Pioglitazone (3 mg center dot kg-1) was administered orally for the last 4 weeks of this diet. At the end of the treatment, serum was collected for biochemical analysis. Levels of PPAR gamma, SOCS-3, pro-inflammatory markers, insulin receptor substrate-2 and Akt/glycogen synthase kinase-3 beta phosphorylation were assesed in rat liver.Key results:Rats fed the HCF diet exhibited hyperlipidemia, hyperinsulinemia, impaired glucose tolerance and insulin resistance. Pioglitazone administration evoked a significant improvement in lipid metabolism and insulin responsiveness. This was accompanied by reduced hepatic expression of SOCS-3, interleukin-6, tumour necrosis factor-alpha and markers of neutrophil infiltration. Diet-induced PPAR gamma expression was unaffected by the pioglitazone treatment.Conclusion and implications:Chronic pioglitazone administration reduced hepatic inflammatory responses in rats fed a HCF diet. These effects were associated with changes in hepatic expression of SOCS-3, which may be a crucial link between the reduced local inflammation and the improved insulin signalling.This article is commented on by Chatterjee, pp. 1889-1891 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2010.00739.x.