Chacón M R, Richart C, Gómez J M, Megía A, Vilarrasa N, Fernández-Real J M, García-España A, Miranda M, Masdevall C, Ricard W, Caubet E, Soler J, Vendrell J
Endocrinology and Diabetes Unit, Research Department, University Hospital of Tarragona Joan XXIII, School of Medicine, University Rovira i Virgili, c/Mallafré Guasch 4, 43007 Tarragona, Spain.
Cytokine. 2006 Feb 7;33(3):129-37. doi: 10.1016/j.cyto.2005.12.005. Epub 2006 Feb 28.
TWEAK, a cytokine of the TNF family, has been found to be expressed under different inflammatory conditions but no data is available concerning the expression of this cytokine and its receptor (Fn14) in human obesity. In the present work we have evaluated the expression of many pro-inflammatory TNF system cytokines (TNF-alpha, TWEAK and their respective receptors, TNFR1, TNFR2 and Fn14) in human adipose tissue of 84 subjects some with different degree of obesity and type 2 diabetes, and its relation with inflammation by also measuring the expression of macrophage marker CD68. We detected expression of TWEAK and Fn14 in isolated mature adipocytes and in the stromovascular fraction. Additionally, we found that LPS upregulates the expression of both genes on THP-1 human monocytic cell line. TWEAK was expressed in adipose tissue of all studied subjects with no differences between obesity group, and was associated with Fn14 expression in morbid obese, mainly in women with type 2 diabetes. The data obtained here also showed that TNF-alpha and TNFR2 mRNAs were significantly more expressed in subcutaneous adipose tissue of subjects with morbid obesity compared to obese and non-obese subjects. In contrast, TNFR1 gene expression was negatively associated with BMI. Our results suggest that the expression of TNF-derived pro-inflammatory cytokines are increased in severe obesity, where macrophage infiltrate could modulate the inflammatory environment through activation of its receptors.
肿瘤坏死因子样弱凋亡诱导因子（TWEAK）是肿瘤坏死因子（TNF）家族的一种细胞因子，已发现在不同炎症条件下均可表达，但关于该细胞因子及其受体（Fn14）在人类肥胖中的表达情况尚无数据。在本研究中，我们评估了84名受试者的人类脂肪组织中多种促炎性TNF系统细胞因子（TNF-α、TWEAK及其各自的受体TNFR1、TNFR2和Fn14）的表达情况，这些受试者中部分患有不同程度的肥胖症和2型糖尿病，我们还通过检测巨噬细胞标志物CD68的表达来研究其与炎症的关系。我们在分离出的成熟脂肪细胞和血管基质部分检测到了TWEAK和Fn14的表达。此外，我们发现脂多糖（LPS）可上调THP-1人单核细胞系中这两种基因的表达。所有研究对象的脂肪组织中均有TWEAK表达，肥胖组之间无差异，且在病态肥胖者中，TWEAK表达与Fn14表达相关，主要是在患有2型糖尿病的女性中。此处获得的数据还表明，与肥胖和非肥胖受试者相比，病态肥胖受试者皮下脂肪组织中TNF-α和TNFR2 mRNA的表达明显更高。相反，TNFR1基因表达与体重指数（BMI）呈负相关。我们的结果表明，在严重肥胖中，TNF衍生的促炎性细胞因子表达增加，巨噬细胞浸润可能通过其受体激活来调节炎症环境。
