Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans
Lipocalin-2 is an inflammatory marker closely associated with obesity, insulin resistance, and hyperglycemia in humans
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DOI：
10.1373/clinchem.2006.075614
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发表时间：
2007-01-01
影响因子：
9.3
通讯作者：
Xu, Aimin
中科院分区：
文献类型：
--
作者：
Wang, Yu;Lam, Karen S. L.;Xu, Aimin
背景：Lipocalin-2是一种分子量为25-kDa的分泌型糖蛋白，是早期检测各种肾损伤的有用生物标志物。由于脂质运载蛋白-2在脂肪组织和肝脏中大量表达，我们研究了其与肥胖相关pathology.Methods的相关性：我们使用实时PCR和内部免疫测定来定量C57 BL/KsJ db/db肥胖小鼠及其年龄和性别匹配的瘦同窝仔中脂质运载蛋白-2的mRNA和血清浓度。我们分析了229人血清脂质运载蛋白-2浓度与各种代谢和炎症变量之间的关系，我们从先前的横断面研究中招募了121名男性和108名女性，评估了胰岛素增敏药物罗格列酮对32名糖尿病患者血清脂质运载蛋白-2浓度的影响结果：与同窝瘦鼠相比，db/db糖尿病/肥胖小鼠脂肪组织和肝脏中脂质运载蛋白-2 mRNA表达水平及其循环浓度均显著升高（P < 0.001）。这些变化在罗格列酮治疗后恢复正常。在人类中，循环脂质运载蛋白-2浓度与肥胖、高脂血症、高血糖和胰岛素抵抗指数呈正相关（P < 0.005），但与HDL胆固醇呈负相关（P = 0.002）。脂质运载蛋白-2浓度与高敏C反应蛋白（hs-CRP）之间也存在强正相关，与年龄、性别和肥胖无关（P = 0.007）。此外，罗格列酮介导的Lipocalin-2浓度降低与胰岛素敏感性增加（r = 0.527; P = 0.002）和hs-CRP浓度降低（r = 0.509; P = 0.003）显著相关。结论：Lipocalin-2是一种与肥胖及其代谢并发症密切相关的炎症标志物。血清脂质运载蛋白-2的测量可能有助于评估肥胖相关代谢和心血管疾病的各种临床干预措施的结果。(c)2007年美国临床化学协会
Background: Lipocalin-2, a 25-kDa secreted glycoprotein, is a useful biomarker for early detection of various renal injuries. Because lipocalin-2 is abundantly expressed in adipose tissue and liver, we investigated its relevance to obesity-related pathologies.Methods: We used real-time PCR and in-house immunoassays to quantify the mRNA and serum concentrations of lipocalin-2 in C57BL/KsJ db/db obese mice and their age- and sex-matched lean littermates. We analyzed the association between serum lipocalin-2 concentrations and various metabolic and inflammatory variables in 229 persons (121 men and 108 women) recruited from a previous cross-sectional study, and we evaluated the effect of the insulin-sensitizing drug rosiglitazone on serum lipocalin-2 concentrations in 32 diabetic patients (21 men and 11 women).Results: Compared with the lean littermates, lipocalin-2 mRNA expression in adipose tissue and liver and its circulating concentrations were significantly increased in db/db diabetic/obese mice (P < 0.001). These changes were normalized after rosiglitazone treatment. In humans, circulating lipocalin-2 concentrations were positively correlated (P < 0.005) with adiposity, hypertriglyceridemia, hyperglycemia, and the insulin resistance index, but negatively correlated (P = 0.002) with HDL cholesterol. There was also a strong positive association between lipocalin-2 concentrations and high sensitivity C-reactive protein (hs-CRP), independent of age, sex, and adiposity (P = 0.007). Furthermore, rosiglitazone-mediated decreases in lipocalin-2 concentrations correlated significantly with increases in insulin sensitivity (r = 0.527; P = 0.002) and decreases in hs-CRP concentrations (r = 0.509; P = 0.003).Conclusions: Lipocalin-2 is an inflammatory marker closely related to obesity and its metabolic complications. Measurement of serum lipocalin-2 might be useful for evaluating the outcomes of various clinical interventions for obesity-related metabolic and cardiovascular diseases. (c) 2007 American Association for Clinical Chemistry