Attenuation of plasma annexin A1 in human obesity
Attenuation of plasma annexin A1 in human obesity
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DOI：
10.1096/fj.12-213728
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发表时间：
2013-01-01
期刊：
影响因子：
4.8
通讯作者：
Renshaw, Derek
中科院分区：
文献类型：
--
作者：
Kosicka, Anna;Cunliffe, Adam D.;Renshaw, Derek
肥胖相关的代谢紊乱的特征在于轻度慢性炎症、白细胞浸润和组织纤维化，这是由膨胀的白色脂肪组织产生脂肪细胞因子所致。膜联蛋白A1（Annexin A1，AnxA 1）是一种内源性糖皮质激素调节的蛋白质，可调节全身性抗炎过程，因此，随着人类肥胖程度的增加而改变。奇怪的是，我们发现血浆AnxA 1浓度与人体受试者的BMI、总体脂百分比和腰臀比呈负相关。血浆AnxA 1也与急性时相蛋白、C反应蛋白（CRP）和脂肪细胞因子瘦素的血浆浓度呈负相关，这表明随着全身炎症的增加，抗炎性AnxA 1减少。此外，AnxA 1基因表达和蛋白质在人脂肪细胞系中的脂肪形成过程中与单独的载体相比显著上调，首次证明AnxA 1从人脂肪细胞中表达和分泌。这些数据表明，内源性抗炎系统未能对由脂肪组织扩张引起的全身性炎症增加做出反应，这是一种与2型糖尿病和心血管疾病的发展密切相关的病症。这些数据提高了血浆AnxA 1减少可能有助于在人类肥胖中观察到的慢性炎症表型的可能性。Kosicka，A.，Cunliffe，A. D、麦肯齐，R.，Gulrez Zariwala，M.，Perretti，M.，弗劳尔河J.，Renshaw，D.肥胖患者血浆膜联蛋白A1的衰减FASEB J.27，368-378（2013）。www.fasebj.org
Obesity-related metabolic disorders are characterized by mild chronic inflammation, leukocyte infiltration, and tissue fibrosis as a result of adipocytokine production from the expanding white adipose tissue. Annexin A1 (AnxA1) is an endogenous glucocorticoid regulated protein, which modulates systemic anti-inflammatory processes and, therefore, may be altered with increasing adiposity in humans. Paradoxically, we found that plasma AnxA1 concentrations inversely correlated with BMI, total percentage body fat, and waist-to-hip ratio in human subjects. Plasma AnxA1 was also inversely correlated with plasma concentrations of the acute-phase protein, C-reactive protein (CRP), and the adipocytokine leptin, suggesting that as systemic inflammation increases, anti-inflammatory AnxA1 is reduced. In addition, AnxA1 gene expression and protein were significantly up-regulated during adipogenesis in a human adipocyte cell line compared to vehicle alone, demonstrating for the first time that AnxA1 is expressed and excreted from human adipocytes. These data demonstrate a failure in the endogenous anti-inflammatory system to respond to increasing systemic inflammation resulting from expanding adipose tissue, a condition strongly linked to the development of type 2 diabetes and cardiovascular disease. These data raise the possibility that a reduction in plasma AnxA1 may contribute to the chronic inflammatory phenotype observed in human obesity.-Kosicka, A., Cunliffe, A. D., Mackenzie, R., Gulrez Zariwala, M., Perretti, M., Flower, R. J., Renshaw, D. Attenuation of plasma annexin A1 in human obesity. FASEB J. 27, 368-378 (2013). www.fasebj.org