一种新的肿瘤坏死因子 (TNF)-α 调节剂，脂多糖诱导的 TNF-α 因子，与肥胖和胰岛素抵抗有关。

A new tumor necrosis factor (TNF)-α regulator, lipopolysaccharides-induced TNF-α factor, is associated with obesity and insulin resistance.

机构信息

Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China.

出版信息

Chin Med J (Engl). 2011 Jan;124(2):177-82.

Abstract

BACKGROUND

Tumor necrosis factor (TNF)-α plays an important role in mediating inflammatory state in obesity and related disorders. Lipopolysaccharides (LPS)-induced TNF-α factor (LITAF) is recently verified as a regulator of TNF-α and other inflammatory cytokines, and maybe act as a transcriptional factor. The aim of this study was to confirm the association between LITAF and obesity and insulin resistance.

METHODS

Forty-seven subjects with a wide range of body mass index (BMI) were included. Subjects were divided into three groups according to the criteria of normal weight, overweight and obese. Anthropometrics and metabolic profile were tested for all the subjects. Peripheral monocytes were isolated and purified. LITAF transcription was detected by real time PCR, and the protein expression in whole cell and nucleus extracts was detected by Western blotting analysis; transcriptional activity of LITAF was detected by ELISA like assay using a probe containing the DNA binding sequence of LITAF. Plasma TNF-α and interleukin (IL)-6 concentrations were determined with ELISA kit.

RESULTS

The LITAF mRNA and protein expression in whole cell were higher in overweight (P < 0.05) and obese group (P < 0.05) compared with that in normal weight group. The LITAF protein expression in the nucleus and transcriptional activity could not be detected. LITAF protein expression was positively correlated with BMI (r = 0.541, P < 0.001), waist circumference (r = 0.391, P = 0.007), the homeostasis model assessment for insulin resistance (r = 0.372, P = 0.011) and fasting insulin levels (r = 0.359, P = 0.013). As a regulator of inflammatory cytokines, LITAF protein expression was positively correlated with plasma TNF-α (r = 0.621, P = 0.002) and IL-6 (r = 0.407, P = 0.039) concentration. Multiple variant regression analysis indicated that BMI (P = 0.002) and waist circumference (P = 0.017) were independent predictors of LITAF protein expression.

CONCLUSIONS

LITAF is associated with obesity and insulin resistance, as well as inflammatory cytokine secretion. The results indicate LITAF to be a new mediator between inflammation and the obesity related disorders.

摘要

背景

肿瘤坏死因子（TNF）-α 在介导肥胖和相关疾病中的炎症状态中发挥重要作用。脂多糖（LPS）诱导的 TNF-α 因子（LITAF）最近被证实是 TNF-α 和其他炎症细胞因子的调节剂，并且可能作为转录因子发挥作用。本研究旨在证实 LITAF 与肥胖和胰岛素抵抗之间的关联。

方法

纳入了 47 名具有广泛体重指数（BMI）的受试者。根据正常体重、超重和肥胖的标准，将受试者分为三组。对所有受试者进行人体测量和代谢特征测试。分离并纯化外周单核细胞。通过实时 PCR 检测 LITAF 转录，通过 Western blot 分析检测全细胞和核提取物中的蛋白表达；通过使用包含 LITAF DNA 结合序列的探针的 ELISA 样测定法检测 LITAF 的转录活性。使用 ELISA 试剂盒测定血浆 TNF-α 和白细胞介素（IL）-6 浓度。

结果

与正常体重组相比，超重（P < 0.05）和肥胖组（P < 0.05）的全细胞 LITAF mRNA 和蛋白表达较高。未检测到核内 LITAF 蛋白表达和转录活性。LITAF 蛋白表达与 BMI（r = 0.541，P < 0.001）、腰围（r = 0.391，P = 0.007）、稳态模型评估的胰岛素抵抗（r = 0.372，P = 0.011）和空腹胰岛素水平（r = 0.359，P = 0.013）呈正相关。作为炎症细胞因子的调节剂，LITAF 蛋白表达与血浆 TNF-α（r = 0.621，P = 0.002）和 IL-6（r = 0.407，P = 0.039）浓度呈正相关。多变量回归分析表明，BMI（P = 0.002）和腰围（P = 0.017）是 LITAF 蛋白表达的独立预测因子。