Serum progranulin concentrations may be associated with macrophage infiltration into omental adipose tissue.
Serum progranulin concentrations may be associated with macrophage infiltration into omental adipose tissue.
复制标题
血清前植物浓度可能与巨噬细胞浸润到胶质脂肪组织中。
作者：
Youn BS;Bang SI;Klöting N;Park JW;Lee N;Oh JE;Pi KB;Lee TH;Ruschke K;Fasshauer M;Stumvoll M;Blüher M
目的：前颗粒蛋白是炎症反应中的重要分子。慢性炎症常与中枢性肥胖和相关紊乱有关；然而，循环前颗粒蛋白在人类肥胖、2型糖尿病和血脂异常中的作用尚不清楚。研究设计和方法：我们建立了一种酶联免疫吸附试验（ELISA）来测定颗粒蛋白前的血清浓度。使用该ELISA，我们在一项横断研究中评估了209名肥胖、体脂分布、胰岛素敏感性和葡萄糖耐量的受试者以及60名正常（NGT）或受损（IGT）葡萄糖耐量或2型糖尿病患者在4周体育训练计划前后的循环前颗粒蛋白。在55名瘦肉或肥胖个体的网膜和皮下脂肪组织（脂肪细胞和间质血管部分细胞）成对样本中，测量了前颗粒蛋白mRNA和蛋白的表达。采用基于thp -1的细胞迁移法测定前颗粒蛋白体外诱导的Erk活化和趋化活性。结果：2型糖尿病患者血清前蛋白浓度明显高于NGT患者和以内脏脂肪堆积为主的肥胖患者。循环颗粒前蛋白与BMI、大网膜脂肪组织巨噬细胞浸润、c反应蛋白（CRP）血清浓度、A1C值和总胆固醇显著相关。多变量线性回归分析显示CRP水平是循环前颗粒蛋白最强的独立预测因子。蛋白前介导的体外趋化程度与单核细胞趋化蛋白-1相似，但不依赖于Gα。此外，在2型糖尿病中，而不是在IGT和NGT个体中，4周的体育训练导致循环前颗粒蛋白水平显著降低。结论：血清颗粒蛋白前浓度升高与内脏型肥胖、血糖升高和血脂异常有关。我们发现前颗粒蛋白是肥胖和2型糖尿病慢性炎症的新标志物，它密切反映了大网膜脂肪组织巨噬细胞的浸润。体育锻炼可显著降低2型糖尿病患者循环前颗粒蛋白升高。
OBJECTIVE—Progranulin is an important molecule in inflammatory response. Chronic inflammation is frequently associated with central obesity and associated disturbances; however, the role of circulating progranulin in human obesity, type 2 diabetes, and dyslipidemia is unknown. RESEARCH DESIGN AND METHODS—For the measurement of progranulin serum concentrations, we developed an enzyme-linked immunosorbent assay (ELISA). Using this ELISA, we assessed circulating progranulin in a cross-sectional study of 209 subjects with a wide range of obesity, body fat distribution, insulin sensitivity, and glucose tolerance and in 60 individuals with normal (NGT) or impaired (IGT) glucose tolerance or type 2 diabetes before and after a 4-week physical training program. Progranulin mRNA and protein expression was measured in paired samples of omental and subcutaneous adipose tissue (adipocytes and cells of the stromal vascular fraction) from 55 lean or obese individuals. Measurement of Erk activation and chemotactic activity induced by progranulin in vitro was performed using THP-1–based cell migration assays. RESULTS—Progranulin serum concentrations were significantly higher in individuals with type 2 diabetes compared with NGT and in obese subjects with predominant visceral fat accumulation. Circulating progranulin significantly correlates with BMI, macrophage infiltration in omental adipose tissue, C-reactive protein (CRP) serum concentrations, A1C values, and total cholesterol. Multivariable linear regression analyses revealed CRP levels as the strongest independent predictor of circulating progranulin. The extent of in vitro progranulin-mediated chemotaxis is similar to that of monocyte chemoattractant protein-1 but independent of Gα. Moreover, in type 2 diabetes, but not in IGT and NGT individuals, physical training for 4 weeks resulted in significantly decreased circulating progranulin levels. CONCLUSIONS—Elevated progranulin serum concentrations are associated with visceral obesity, elevated plasma glucose, and dyslipidemia. We identified progranulin as a novel marker of chronic inflammation in obesity and type 2 diabetes that closely reflects omental adipose tissue macrophage infiltration. Physical training significantly reduces elevated circulating progranulin in patients with type 2 diabetes.
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影响因子：
64.8
作者：
Cruts, Marc;Gijselinck, Ilse;Van Broeckhoven, Christine
通讯作者：
Van Broeckhoven, Christine
影响因子：
82.9
作者：
He, ZH;Ong, CHP;Bateman, A
通讯作者：
Bateman, A
DOI：
10.1073/pnas.0601752103
发表时间：
2006-04-25
影响因子：
11.1
作者：
Gesta, S;Blüher, M;Kahn, CR
通讯作者：
Kahn, CR
影响因子：
29
作者：
Kloeting, Nora;Graham, Timothy E.;Kahn, Barbara B.
通讯作者：
Kahn, Barbara B.
影响因子：
5.8
作者：
Bruun, JM;Lihn, AS;Richelsen, B
通讯作者：
Richelsen, B