Conflict of Interest Statement: The authors declare that there is no duality of interest associated with this manuscript.
Obesity-induced renal impairment is exacerbated in interleukin-6-knockout mice
Article first published online: 23 FEB 2012
© 2011 The Authors. Nephrology © 2011 Asian Pacific Society of Nephrology
Volume 17, Issue 3, pages 257–262, March 2012
How to Cite
HARCOURT, B. E., FORBES, J. M. and MATTHEWS, V. B. (2012), Obesity-induced renal impairment is exacerbated in interleukin-6-knockout mice. Nephrology, 17: 257–262. doi: 10.1111/j.1440-1797.2011.01547.x
- Issue published online: 23 FEB 2012
- Article first published online: 23 FEB 2012
- Accepted manuscript online: 30 NOV 2011 07:49AM EST
- Accepted for publication 3 November 2011.; Accepted manuscript online 30 November 2011.
- collagen IV;
- high-fat feeding;
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-β1) 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-β1, 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.