AIM: Interleukin-6 (IL-6) is secreted from adipose tissue and thought to contribute to obesity-related disorders. The aim of this study was to assess if IL-6-knockout (IL-6-/-) mice would develop obesity-induced renal impairment. METHODS: Wild-type (WT) and IL-6-/- mice were high-fat fed (HFF) for 16 weeks to induce obesity. At the end of the study, renal function was measured via albumin/creatinine ratio and serum creatinine levels, using enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC). Glomerulosclerotic index (GSI) was scored in periodic acid Schiff-stained sections and collagen IV accumulation was assessed by immunohistochemistry. Renal cortical tumour growth factor beta (TGF-β(1) ) activity and monocyte chemotactic protein-1 (MCP-1) levels were measured via ELISA. RESULTS: Renal IL-6 concentrations were increased with obesity. Although both WT HFF and IL-6-/- HFF mice exhibited renal impairment as measured by increased serum creatinine and urinary albumin/creatinine ratios, this was exacerbated in IL-6-/- mice. Obese mice had renal activation of cortical TGF-β(1) , which was also higher in IL-6-/- mice. Collagen IV staining was not affected by obesity. GSI was increased with obesity in both WT and IL-6-/- mice. CONCLUSION: Obese IL-6-/- mice demonstrated renal functional and structural abnormalities above that seen in obese WT mice. We suggest that absence or low IL-6 levels may be an important accelerating factor implicated in the development and progression of obesity-induced renal disease.
AIM: Interleukin-6 (IL-6) is secreted from adipose tissue and thought to contribute to obesity-related disorders. The aim of this study was to assess if IL-6-knockout (IL-6-/-) mice would develop obesity-induced renal impairment. METHODS: Wild-type (WT) and IL-6-/- mice were high-fat fed (HFF) for 16 weeks to induce obesity. At the end of the study, renal function was measured via albumin/creatinine ratio and serum creatinine levels, using enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC). Glomerulosclerotic index (GSI) was scored in periodic acid Schiff-stained sections and collagen IV accumulation was assessed by immunohistochemistry. Renal cortical tumour growth factor beta (TGF-β(1) ) activity and monocyte chemotactic protein-1 (MCP-1) levels were measured via ELISA. RESULTS: Renal IL-6 concentrations were increased with obesity. Although both WT HFF and IL-6-/- HFF mice exhibited renal impairment as measured by increased serum creatinine and urinary albumin/creatinine ratios, this was exacerbated in IL-6-/- mice. Obesemice had renal activation of cortical TGF-β(1) , which was also higher in IL-6-/- mice. Collagen IV staining was not affected by obesity. GSI was increased with obesity in both WT and IL-6-/- mice. CONCLUSION:ObeseIL-6-/- mice demonstrated renal functional and structural abnormalities above that seen in obese WT mice. We suggest that absence or low IL-6 levels may be an important accelerating factor implicated in the development and progression of obesity-induced renal disease.