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Obesity‐induced renal impairment is exacerbated in interleukin‐6‐knockout mice
Author(s) -
HARCOURT BROOKE E,
FORBES JOSEPHINE M,
MATTHEWS VANCE B
Publication year - 2012
Publication title -
nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 61
eISSN - 1440-1797
pISSN - 1320-5358
DOI - 10.1111/j.1440-1797.2011.01547.x
Subject(s) - medicine , endocrinology , creatinine , renal function , obesity , albumin , adipose tissue , interleukin , cytokine
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.

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