Catalán Victoria, Gómez-Ambrosi Javier, Rodríguez Amaia, Ramírez Beatriz, Valentí Víctor, Moncada Rafael, Silva Camilo, Salvador Javier, Frühbeck Gema
Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain,
Genes Nutr. 2015 May;10(3):460. doi: 10.1007/s12263-015-0460-8. Epub 2015 Apr 14.
Inflammation is a critical contributor to the pathogenesis of metabolic disorders with adipose tissue being crucial in the inflammatory response by releasing multiple adipokines with either pro- or anti-inflammatory activities with potential functions as metabolic regulators. Peripheral blood mononuclear cells (PBMC) have been proposed as representative of the inflammatory status in obesity. The aim of the present study was to evaluate the contribution of PBMC to the obesity-associated chronic inflammation analyzing the expression of novel adipokines. Samples obtained from 69 subjects were used in the study. Real-time PCR determinations were performed to quantify gene expression levels in PBMC of novel adipokines including chemerin, chitinase-3-like protein 1 (YKL-40), lipocalin-2 (LCN-2) and osteopontin (OPN), and their circulating concentrations were also determined by ELISA. We show, for the first time, that PBMC gene expression levels of chemerin (P < 0.0001), chitinase-3-like protein 1 (P = 0.010), lipocalin-2 (P < 0.0001) and osteopontin (P < 0.0001) were strongly upregulated in obesity independently of the glycemic state. Circulating concentrations of these adipokines followed the same trend being significantly higher (P < 0.05) in obese normoglycemic and type 2 diabetic patients compared to lean volunteers and also associated (P < 0.05) with their corresponding mRNA levels in PBMC. These results provide evidence that alterations in inflammation-related adipokines are manifest in PBMC, which might contribute to the low-grade chronic inflammation that characterizes obesity.
炎症是代谢紊乱发病机制的关键因素,脂肪组织通过释放多种具有促炎或抗炎活性且可能具有代谢调节功能的脂肪因子,在炎症反应中起关键作用。外周血单核细胞(PBMC)已被认为是肥胖炎症状态的代表。本研究的目的是通过分析新型脂肪因子的表达来评估PBMC对肥胖相关慢性炎症的作用。研究使用了从69名受试者获得的样本。进行实时PCR测定以量化PBMC中新型脂肪因子的基因表达水平,这些脂肪因子包括chemerin、几丁质酶-3样蛋白1(YKL-40)、lipocalin-2(LCN-2)和骨桥蛋白(OPN),并且还通过ELISA测定它们的循环浓度。我们首次表明,肥胖时chemerin(P < 0.0001)、几丁质酶-3样蛋白1(P = 0.010)、lipocalin-2(P < 0.0001)和骨桥蛋白(P < 0.0001)的PBMC基因表达水平强烈上调,且与血糖状态无关。这些脂肪因子的循环浓度呈现相同趋势,与瘦志愿者相比,肥胖血糖正常和2型糖尿病患者的循环浓度显著更高(P < 0.05),并且也与PBMC中相应的mRNA水平相关(P < 0.05)。这些结果提供了证据,表明炎症相关脂肪因子的改变在PBMC中表现明显,这可能导致肥胖所特有的低度慢性炎症。