title: Obesity Is a Positive Modulator of IL-6R and IL-6 Expression in the Subcutaneous Adipose Tissue: Significance for Metabolic Inflammation.
abstract: 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.
authors.affiliation: Immunology and Innovative Cell Therapy Unit, Dasman Diabetes Institute (DDI), P.O. Box 1180, Dasman, Kuwait.
authors.forename: Sardar
authors.initials: S
authors.lastname: Sindhu
authors.affiliation: Immunology and Innovative Cell Therapy Unit, Dasman Diabetes Institute (DDI), P.O. Box 1180, Dasman, Kuwait.
authors.forename: Reeby
authors.initials: R
authors.lastname: Thomas
authors.affiliation: Immunology and Innovative Cell Therapy Unit, Dasman Diabetes Institute (DDI), P.O. Box 1180, Dasman, Kuwait.
authors.forename: Puthiyaveetil
authors.initials: P
authors.lastname: Shihab
authors.affiliation: Tissue Bank Core Facility, Dasman Diabetes Institute (DDI), P.O. Box 1180, Dasman, Kuwait.
authors.forename: Devarajan
authors.initials: D
authors.lastname: Sriraman
authors.affiliation: Immunology and Innovative Cell Therapy Unit, Dasman Diabetes Institute (DDI), P.O. Box 1180, Dasman, Kuwait; Tissue Bank Core Facility, Dasman Diabetes Institute (DDI), P.O. Box 1180, Dasman, Kuwait.
authors.forename: Kazem
authors.initials: K
authors.lastname: Behbehani
authors.affiliation: Immunology and Innovative Cell Therapy Unit, Dasman Diabetes Institute (DDI), P.O. Box 1180, Dasman, Kuwait.
authors.forename: Rasheed
authors.initials: R
authors.lastname: Ahmad
mesh_terms: D000328:Adult; D000368:Aged; D015992:Body Mass Index; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D015850:Interleukin-6 / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D019947:Receptors, Interleukin-6 / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050151:Subcutaneous Fat / Q000378:metabolism* / Q000473:pathology
chemical_list: C508600:IL6 protein, human; C508603:IL6R protein, human; D015850:Interleukin-6; D019947:Receptors, Interleukin-6