Obesity Is a Positive Modulator of IL-6R and IL-6 Expression in the Subcutaneous Adipose Tissue: Significance for Metabolic Inflammation

The role of IL-6R/IL-6 axis in metabolic inflammation remains controversial. We determined the changes in adipose tissue expression of IL-6R and IL-6 in obese, overweight, and lean non-diabetic individuals. Subcutaneous adipose tissue biopsies were collected from 33 obese, 22 overweight, and 10 lean individuals and the expression of IL-6R, IL-6, TNF-alpha, MCP-1, IP-10, CD11b, CD163, and CD68 was detected by immunohistochemistry; results were also confirmed by real-time RT-PCR and confocal microscopy. The data were compared using unpaired t-test and the dependence between two variables was assessed by Pearson's correlation test. Obese individuals showed higher IL-6R expression (103.8 +/- 4.807) in the adipose tissue as compared with lean/overweight (68.06 +/- 4.179) subjects (P<0.0001). The elevated IL-6R expression correlated positively with body mass index (BMI) (r=0.80 P< 0.0001) and percent body fat (r=0.69 P=0.003). The increased IL-6R expression in obesity was also confirmed by RT-PCR (Obese: 3.921 +/- 0.712 fold; Lean/ Overweight: 2.191 +/- 0.445 fold; P=0.0453) and confocal microscopy. IL-6 expression was also enhanced in obese adipose tissue (127.0 +/- 15.91) as compared with lean/overweight (86.69 +/- 5.25) individuals (P=0.03) which correlated positively with BMI (r=0.58 P=0.008). IL-6 mRNA expression was concordantly higher in obese (16.60 +/- 2.214 fold) versus lean/overweight (9.376 +/- 1.656 fold) individuals (P=0.0108). These changes in the IL-6R/IL-6 expression correlated positively with the adipose tissue expression of CD11b (IL-6R r=0.44 P=0.063; IL-6 r=0.77 P< 0.0001), CD163 (IL-6R r=0.45 P=0.045; IL-6 r=0.55 P=0.013), TNF-alpha (IL-6R r=0.73 P=0.0003; IL-6 r=0.60 P=0.008), MCP-1 (IL-6R r=0.61 P=0.005; IL-6 r=0.63 P=0.004) and IP-10 (IL-6R r=0.41 P=0.08; IL-6 r=0.50 P=0.026). It was, therefore, concluded that obesity was a positive modulator of IL-6R and IL-6 expression in the adipose tissue which might be a contributory mechanism to induce metabolic inflammation.