Visfatin, TNF-α and IL-6 mRNA Expression is Increased in Mononuclear Cells from Type 2 Diabetic Women

Abstract

Visfatin, is a new adipokine, highly expressed in the visceral fat of both mice and humans. To examine whether visfatin is expressed in human peripheral monocyte-enriched mononuclear cells and whether its expression is altered in type 2 diabetes (DM2), we compared 24 DM2 women [17 overweight (BMI >25) and 7 lean (BMI<25)] to 26 healthy women (14 overweight and 12 lean), all premenopausal. Relative visfatin mRNA levels were significantly higher (approximately 3-fold) in DM2 compared to healthy control women (p<0.02), independently of the presence of overweight/obesity. Mononuclear TNF-alpha and IL-6 mRNA expression was also elevated in DM2 compared to control women (p=0.001 and p=0.004, respectively), an increase observed in both lean and overweight DM2 women. By contrast, circulating visfatin, TNF-alpha, and IL-6 levels showed no difference between DM2 and control women, while adiponectin plasma levels were significantly decreased in the DM2 women (p<0.001). Circulating visfatin and TNF-alpha levels did not differ either between the lean and the overweight subgroups of DM2 and control women, while IL-6 plasma levels were significantly higher in both overweight subgroups compared to their lean counterparts. In conclusion, visfatin, TNF-alpha, and IL-6 mRNA expressions are increased in peripheral mononuclear-monocytic cells from women with type 2 diabetes, independent of their BMI, which may enhance the effects of their adipose-derived levels and may contribute to the increased insulin resistance and atherogenic risk of these patients.

Association of increased Visfatin/PBEF/NAMPT circulating concentrations and gene expression levels in peripheral blood cells with lipid metabolism and fatty liver in human morbid obesity

“…Our study provides evidence that obese patients exhibit upregulated NAMPT mRNA expression levels in PBC, contrasting with previously published results where a negative or no correlation with BMI was detected [39,46]. However, a positive correlation has been shown with waist circumference measures, a better indicator of visceral obesity [46]. The lack of association between the circulating concentrations and the mRNA expression levels of NAMPT in PBC, omental adipose tissue and liver suggests that other organs or cell types, including bone marrow or muscle [11], may be contributing to the increased NAMPT levels in obesity.…”

“…The dimerization of visfatin may have functional implications, particularly in regard to its NADþ biosynthetic enzyme function that has been shown to depend on dimerization and to be active also in the extracellular space [44]. Our study provides evidence that obese patients exhibit upregulated NAMPT mRNA expression levels in PBC, contrasting with previously published results where a negative or no correlation with BMI was detected [39,46]. However, a positive correlation has been shown with waist circumference measures, a better indicator of visceral obesity [46].…”

“…The association of NAMPT with other inflammatory markers, such as MCP-1 and PAI-1 antigen [57] together with its increased production and release by macrophages [28,58] supports its pro-inflammatory properties [59]. Furthermore, a strong association between NAMPT and TNF-a and IL-8 in PBC has been described [39,46,58]. However, Varma et al [19] found a negative association between NAMPT and CD68 as well as TNF-a in adipose tissue, suggesting an antiinflammatory role for NAMPT.…”

Diverse Pattern of Cytokine Production, their Functional Association and mRNA Expression in Tuberculosis Patients with Diabetes Mellitus and their Household Contacts

“…The G allele or GG genotype in the IL-6 gene promoter region (-174), was associated with high IL-6 production in TB patients which may have promoted TB by inhibiting production of other cytokines like TNF and IL-1β which was dissimilar to our study where GG genotype was associated with low IL-6 production in PTB patients [43,44]. Selvaraj et al, has not reported any significant association between the genotypes of IL-6 -174G>C polymorphisms and production both in PTB and HCs unlike our study population [45]. Studies have not been reported in TBDM, TBDM HHC, PTB HHC and DM.…”

Slc27a2 expression in peripheral blood mononuclear cells as a molecular marker for overweight development

“…16,17 Some evidence in humans indicates that obesity and insulin resistance are associated with activation of these cells and with changes in the expression of a variety of cytokines related to inflammation and the immune response, such as interleukin-6 and tumor necrosis factor-a. 15,18,19 Moreover, PBMC express molecules related with energy homeostasis that are altered in the obese state, such as leptin, visfatin and resistin, [20][21][22] and their expression profile responds to differences in nutrient status. 23,24 Several gene expression studies using microarray analysis have assessed a differential expression in genetically and diet-induced obese animals, but most of them explored adipose tissue.…”