Proinflammatory cytokines in obesity:: Impact of type 2 diabetes mellitus and gastric bypass

Background: Obesity and obesity-associated type 2 diabetes mellitus (T2DM) are frequently related to a low-grade chronic inflammatory state, which increases the risk of developing cardiovascular diseases. The aim of the present work was to evaluate the effect of obesity and T2DM on the concentrations of pro-inflammatory factors and to study the effect of weight loss after Roux-en-Y gastric bypass (RYGBP). Methods: Plasma concentrations of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-a (TNF-alpha), serum amyloid A (SAA) and sialic acid (SA) were measured in 25 female volunteers. The concentrations of these cytokines were determined in 14 female obese patients before and after weight loss following RYGBP. Additionally, visceral adipose tissue (VAT) obtained from 15 females was used to quantify expression levels of MCP-1 and CD68 by Real-Time PCR. Results: Both obese normoglycemic (NG) and T2DM groups exhibited significantly higher MCP-1 (P < 0.05), TNF-alpha (P < 0.01), SAA (Pww < 0.05) and SA (P < 0.05) concentrations, compared to the lean group. No differences were found between obese NG and obese T2DM subjects. A significant positive correlation was found between body fat percentage (BF) and all inflammatory markers (P < 0.05) studied. MCP-1 expression levels in VAT were upregulated in obese NG (P=0.008) and obese T2DM (P=0.032) patients compared to lean subjects, but no additional detrimental effect of T2DM was observed between both obese groups. After weight loss, SAA (P < 0.001) and SA (P < 0.05) concentrations diminished, whereas circulating levels of MCP-1 showed a tendency to decrease (P=0.093) and TNF-alpha did not change. Conclusion: The present findings suggest that elevated pro-inflammatory cytokine levels found in obese patients relate mainly to obesity rather than to T2DM. Moreover, surgery-induced weight loss reduces circulating concentrations of key pro-inflammatory factors, which contribute to the improvement in the cardiovascular co-morbidity following excess weight loss.