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

• Published in: PloS one Vol. 10; no. 7; p. e0133494
• Main Authors: Sindhu, Sardar, Thomas, Reeby, Shihab, Puthiyaveetil, Sriraman, Devarajan, Behbehani, Kazem, Ahmad, Rasheed
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 22.07.2015; Public Library of Science (PLoS)
• Subjects: Adipocytes; Adipose tissue; Adult; Aged; Angiogenesis; Antigens; Biopsy; Body composition; Body fat; Body mass; Body Mass Index; Body size; Body weight; Cardiovascular disease; CD11b antigen; CD163 antigen; Comparative analysis; Confocal microscopy; Correlation; Cytokines; Diabetes; Diabetes mellitus; Fasting; Female; Gene expression; Gene Expression Regulation; Glucose; Humans; Immunohistochemistry; Immunology; Inflammation; Inflammation - metabolism; Inflammation - pathology; Insulin resistance; Interleukin 6; Interleukin-6 - biosynthesis; IP-10 protein; Lipids; Male; Metabolism; Microscopy; Middle Aged; Monocyte chemoattractant protein 1; Obesity; Obesity - metabolism; Obesity - pathology; Overweight; Polymerase chain reaction; Proteins; Receptors, Interleukin-6 - biosynthesis; Reverse Transcriptase Polymerase Chain Reaction; RNA; Rodents; Subcutaneous Fat - metabolism; Subcutaneous Fat - pathology; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0133494

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-α, 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-α (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.