S100A8

Calprotectin, a novel marker of obesity, has recently gained attention for its potential role in insulin resistance and inflammation. This study aimed to evaluate the circulating levels and tissue expression of calprotectin subunits (S100A8 and S100A9) in visceral adipose tissue (VAT) and investigate their impact on obesity, insulin resistance, and inflammation, as well as the effects of weight loss. The study included 53 subjects, and gene expression levels of the S100A8/A9 complex were analyzed in VAT, adipocytes, and stromal vascular fraction cells (SVFCs). Circulating levels of calprotectin and soluble receptor for advanced glycation end products (sRAGE) were measured before and after weight loss through Roux-en-Y gastric bypass (RYGB) (n = 26). The results showed that circulating calprotectin levels and VAT expression of the S100A8/A9 complex were significantly higher in both normoglycemic and type 2 diabetic obese patients, with a strong correlation to inflammatory markers. In contrast, sRAGE levels were significantly lower in obese groups compared to lean controls. Following RYGB, calprotectin levels decreased significantly, while sRAGE levels showed a trend toward increase. Expression of calprotectin was primarily found in SVFCs, with significant correlation to the mRNA levels of monocyte-macrophage-related molecules, including CD68, MCP1, CD11B, and NOX2. Furthermore, TNF-α treatment increased S100A8 expression in human visceral adipocytes. The elevated levels of calprotectin in obesity and type 2 diabetes, along with its association with inflammation and higher expression in SVFCs, suggest that calprotectin may act as a chemotactic factor, contributing to macrophage recruitment in VAT and exacerbating inflammation, which may drive obesity-associated comorbidities.