Expression of caveolin-1 in human adipose tissue is upregulated in obesity and obesity-associated type 2 diabetes mellitus and related to inflammation

Expression of caveolin-1 in human adipose tissue is upregulated in obesity and obesity-associated type 2 diabetes mellitus and related to inflammation
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DOI:
10.1111/j.1365-2265.2007.03021.x
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发表时间:
2008-02-01
影响因子:
3.2
通讯作者:
Fruehbeck, Gema
Fruehbeck, Gema
中科院分区:
医学3区
文献类型:
--
作者:
Catalan, Victoria;Gomez-Ambrosi, Javier;Fruehbeck, Gema

文献摘要

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目的小窝蛋白-1(CAV-1)在细胞生物学的许多方面发挥重要作用,包括囊泡转运、胆固醇稳态和信号转导。本研究的目的是探讨肥胖和肥胖相关的2型糖尿病(T2 DM)患者脂肪组织中CAV-1的基因表达水平,并分析其在肥胖相关炎症状态中的潜在意义。设计和方法研究中使用了从15名女性获得的内脏脂肪组织(VAT)和皮下脂肪组织(SAT)。患者被分为瘦型(BMI 20.8 +/- 1.0 kg/m2)或肥胖型(BMI 50.5 +/- 2.6 kg/m2)。肥胖组进一步细分为血糖正常(NG)或T2 DM患者。人体测量以及循环代谢物,激素和脂肪因子进行了测定。实时荧光定量PCR(Real-time polymerase chain reaction,PCR)检测VAT和SAT中CAV-1和单核细胞趋化蛋白(monocyte chemoattractant protein,MCP-1)的表达。肥胖NG和T2 DM患者VAT和SAT中CAV-1的表达水平均显著高于消瘦者(P < 0.05)。肥胖NG和T2 DM患者之间的VAT无差异。肥胖T2 DM患者SAT中CAV-1表达水平高于肥胖NG患者(P < 0.05)。VAT中CAV-1 mRNA表达水平与不同的循环炎症标志物如唾液酸(SA)显著相关(P < 0.001)和纤维蛋白原MCP 1 mRNA表达水平与对照组相比,差异有显著性(P < 0.001结论本研究首次发现CAV-1基因mRNA表达上调,提示CAV-1基因mRNA表达上调可能与CAV-1基因mRNA表达上调有关。与瘦对照相比,肥胖NG和肥胖T2 DM患者的VAT和SAT中CAV-1的表达水平表明CAV-1在肥胖和T2 DM发展中的作用。与不同炎症标志物的关联进一步表明CAV-1在伴随肥胖的低度炎症中的意义。
Objective Caveolin-1 (CAV-1) plays important roles in many aspects of cellular biology, including vesicular transport, cholesterol homeostasis and signal transduction. The aim of the present study was to explore gene expression levels of CAV-1 in human adipose tissue in obesity and obesity-associated type 2 diabetes mellitus (T2DM) and to analyse its potential implication in the inflammatory state associated with obesity.Design and methods Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) obtained from 15 females were used in the study. Patients were classified as lean (BMI 20.8 +/- 1.0 kg/m(2)) or obese (BMI 50.5 +/- 2.6 kg/m(2)). The obese group was further subclassified as normoglycaemic (NG) or patients with T2DM. Anthropometric measurements as well as circulating metabolites, hormones and adipokines were determined. Real-time polymerase chain reaction (PCR) analyses were performed to quantify transcript levels of CAV-1 and monocyte chemoattractant protein (MCP-1).Results The presence of CAV-1 protein was detected in VAT and SAT by immunohistochemistry. Both obese NG and with T2DM patients exhibited significantly higher CAV-1 expression levels in VAT and SAT compared with lean subjects (P < 0.05). No differences between obese NG and T2DM patients were observed in VAT. However, obese T2DM patients were found to have higher CAV-1 expression levels in SAT (P < 0.05) compared with obese NG patients. A significant correlation was found between CAV-1 mRNA expression levels in VAT and different circulating inflammatory markers such as sialic acid (SA) (P < 0.001) and fibrinogen (P < 0.001) as well as with MCP1 mRNA expression (P < 0.05).Conclusion Our findings show for the first time the upregulation of mRNA CAV-1 expression levels in VAT and SAT of obese NG and obese T2DM patients compared with lean controls, suggesting a role for CAV-1 in obesity and T2DM development. The association with different inflammatory markers further suggests an implication of CAV-1 in the low-grade inflammation accompanying obesity.