title: Obesity-induced renal impairment is exacerbated in interleukin-6-knockout mice.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Glycation and Diabetes Complications, Monash University, Melbourne, Victoria, Australia. brooke.harcourt@bakeridi.edu.au
authors: Brooke E
authors: BE
authors: Harcourt
authors: Josephine M
authors: JM
authors: Forbes
authors: Vance B
authors: VB
authors: Matthews
mesh_terms: D000818:Animals; D059305:Diet, High-Fat; D015850:Interleukin-6 / Q000235:genetics / Q000502:physiology*; D007668:Kidney / Q000473:pathology / Q000502:physiology; D007674:Kidney Diseases / Q000209:etiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000150:complications*; D015398:Signal Transduction
chemical_list: D015850:Interleukin-6