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 intothree 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 i
The molecular mechanism by which obesity induces insulin resistance is not completely understood.The aim of this study was to determine how lipopolysaccharide-induced tumor necrosis-α factor (LITAF) influenced obesity-induced insulin resistance using a cellular co-culture system.The cells were divided into 3 groups:palmitic acid (PA) stimulation group,LITAF small interfering RNA (siRNA) group and untreated (NC) group.The LITAF siRNA was used for knockdown of LITAF ex-pression in human THP-1 macrophages.The expression levels of LITAF,IRS-2,IRS-2Tyr465,PI3K,and GLUT2 in each group were measured by using quantitative reverse transcriptase real-time poly-merase chain reaction and Western blotting.The expression of LITAF was much higher in the PA group than in the siRNA and NC groups (P<0.05);meanwhile,the expression of IRS-2,IRS-2Tyr465,PI3K,and GLUT2 was much lower in the PA group than in the NC group (P<0.05);however,IRS-2,IRS-2Tyr465,PI3K,and GLUT2 had much higher expression in the siRNA group than in the PA group (P<0.05).It is concluded that PA can induce insulin resistance in liver cells and knockdown of LITAF expression can reduce insulin resistance in liver cells,suggesting LITAF may regulate the insulin signal transduction pathway involved in obesity-induced insulin resistance.
SUMO4 Met55Val variation was shown to be related to type 2 diabetes susceptibility and the vascular complications in Asian people.To further examine the related mechanisms,this study was designed to evaluate the association of SUMO4 Met55Val polymorphism with insulin resistance and β cell function in newly diagnosed type 2 diabetic patients in a Chinese population.Four hundred and twenty seven newly diagnosed type 2 diabetic patients were selected for SUMO4 Met55Val polymorphism genotype analysis.All subjects underwent a 75-g oral glucose tolerance test（OGTT） to estimate the insulin sensitivity and β cell function.Anthropometrics and a metabolic profile were used for phenotyping analysis.The results showed that the SUMO4 Met55Val polymorphism was associated with higher insulin resistance（P0.001） and lower insulin sensitivity（P0.001）.Patients with GG genotype had higher levels of plasma glucose,insulin and C peptide.Insulin sensitivity index（ISI） was closely correlated with body mass index（BMI） in patients with GG genotype in comparison to the counterparts with AG or AA genotype（r=-0.504 vs.r=-0.430 vs.r=-0.340）.Multiple regression linear analysis showed that SUMO4 Met55Val polymorphism was an independent determinant for insulin sensitivity（P=0.001）,which,along with triglyceride,BMI and sex,could account for 20.1% of the variation in ISI.The result remained the same after adjusting for BMI and sex.No association was found between SUMO4 Met55Val polymorphism and β cell function（all P0.05）.It was concluded that SUMO4 Met55Val variant was associated with increased insulin resistance in Chinese patients with newly diagnosed type 2 diabetes.
