Obesity-induced renal impairment is exacerbated in interleukin-6-knockout mice

  1. BROOKE E HARCOURT1,3,*,
  2. JOSEPHINE M FORBES1,3,
  3. VANCE B MATTHEWS2,4

Article first published online: 23 FEB 2012

DOI: 10.1111/j.1440-1797.2011.01547.x

Issue

Nephrology

Nephrology

Volume 17, Issue 3, pages 257–262, March 2012

Additional Information

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

Author Information

  1. 1

    Glycation and Diabetes Complications

  2. 2

    Cellular and Molecular Metabolism Laboratory, Baker IDI Heart and Diabetes Research Institute

  3. 3

    Department of Immunology and Medicine, Monash University, AMREP, Melbourne, Victoria

  4. 4

    UWA Centre for Medical Research, The Western Australian Institute for Medical Research, Perth, Western Australian, Australia

*Dr Brooke E Harcourt, Glycation and Diabetes Complications, Baker IDI, PO Box 6492, St Kilda Road Central, Melbourne, Vic. 8008, Australia. Email: brooke.harcourt@bakeridi.edu.au

  1. Conflict of Interest Statement: The authors declare that there is no duality of interest associated with this manuscript.

Publication History

  1. Issue published online: 23 FEB 2012
  2. Article first published online: 23 FEB 2012
  3. Accepted manuscript online: 30 NOV 2011 07:49AM EST
  4. Accepted for publication 3 November 2011.; Accepted manuscript online 30 November 2011.

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Keywords:

  • collagen IV;
  • high-fat feeding;
  • IL-6;
  • IL-6-/-;
  • nephropathy;
  • obesity

ABSTRACT:

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.

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