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

作者：Ji Zhen-zhong; Dai Zhe; Xu Yan-cheng^*

来源：Chinese Medical Journal, 2011, 124(2): 177-182.

DOI：10.3760/cma.j.issn.0366-6999.2011.02.004

• obesity
• insulin resistance
• lipopolysaccharides-induced TNF-alpha factor
• TNF-alpha

Background Tumor necrosis factor (TNF)-alpha plays an important role in mediating inflammatory state in obesity and related disorders. Lipopolysaccharides (LPS)-induced TNF-alpha factor (LITAF) is recently verified as a regulator of TNF-alpha 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-alpha 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-alpha (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. Chin Med J 2011;124(2):177-182

• 出版日期2011-1-20
• 单位武汉大学