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.
Highlights
With the increasing use of energy-rich foods and overnutrition worldwide, the incidence of obesity has risen to epidemic proportions and the risks for obesity-associated diseases are escalating in all age groups [1]
To see whether the changes in IL-6 receptor (IL-6R) protein expression were corroborated at the gene expression level, we used real-time reverse-transcription polymerase chain reaction (RT-PCR) and, as expected, we found that IL-6R mRNA expression was significantly elevated in obese individuals (3.921 ±0.712 fold) as compared with lean and overweight (2.191±0.445 fold) subjects (P = 0.0453) (Fig 2B)
Our data show the elevated adipose tissue expression of IL-6R and IL-6 in obese individuals and the changes correlate with clinical indicators of obesity including body mass index (BMI) and percentage of body fat (PBF)
Summary
With the increasing use of energy-rich foods and overnutrition worldwide, the incidence of obesity has risen to epidemic proportions and the risks for obesity-associated diseases are escalating in all age groups [1]. The white adipose tissue is a site for energy storage but is an active endocrine organ that secretes over 50 cyto-/chemokines and bioactive mediators called adipokines which are involved in lipid metabolism, insulin sensitivity, immunity, angiogenesis, and inflammation [2,3]. Interleukin (IL)-6 is an important cytokine which is secreted by macrophages, adipocytes, and other sources including skeletal muscle, fibroblasts, and endothelial cells [5,6]. It is a systemic regulator of body weight and lipid metabolism [7,8]. We present the data showing that obesity enhances gene and protein expression of the IL-6R and IL-6 in the human subcutaneous adipose tissue which correlates positively with the local expression of several inflammatory markers
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