Attenuation of inflammation and cellular stress-related pathways maintains insulin sensitivity in obese type I interleukin-1 receptor knockout mice on a high-fat diet

Baukje de Roos, Vanessa Rungapamestry, Karen Ross, Garry Rucklidge, Martin Reid, Gary Duncan, Graham Horgan, Sinead Toomey, John Browne, Christine E. Loscher, Kingston H. G. Mills, Helen M. Roche

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39 Citations (Scopus)

Abstract

The development of insulin resistance in the obese is associated with chronic, low-grade inflammation. We aimed to identify novel links between obesity, insulin resistance and the inflammatory response by comparing C57BL/6 with type I interleukin-1 receptor knockout (IL-1RI(-/-)) mice, which are protected against diet-induced insulin resistance. Mice were fed a high-fat diet for 16 wk. Insulin sensitivity was measured and proteomic analysis was performed on adipose, hepatic and skeletal muscle tissues. Despite an equal weight gain, IL-1RI(-/-) mice had lower plasma glucose, insulin and triacylglycerol concentrations, compared with controls, following dietary treatment. The higher insulin sensitivity in IL-1RI(-/-) mice was associated with down-regulation of antioxidant proteins and proteasomes in adipose tissue and hepatic soluble epoxide hydrolase, consistent with a compromised inflammatory response as well as increased glycolysis and decreased fatty acid beta-oxidation in their muscle. Their lower hepatic triacylglycerol concentrations may reflect decreased flux of free fatty acids to the liver, decreased hepatic fatty acid-binding protein expression and decreased lipogenesis. Correlation analysis revealed down-regulation of classical biomarkers of ER stress in their adipose tissue, suggesting that disruption of the IL-1RI-mediated inflammatory response may attenuate cellular stress, which was associated with significant protection from diet-induced insulin resistance, independent of obesity.
Original languageEnglish
Pages (from-to)3244-3256
Number of pages13
JournalProteomics
Volume9
Issue number12
DOIs
Publication statusPublished - Jun 2009

Keywords

  • adipose tissue
  • animals
  • chemokine CCL2
  • epididymis
  • epoxide hydrolases
  • inflammation
  • insulin resistance
  • liver
  • male
  • membrane proteins
  • mice
  • mice, inbred C57BL
  • mice, knockout
  • mice, obese
  • muscle, skeletal
  • obesity
  • principal component analysis
  • proteome
  • proteomics
  • receptors, interleukin-1
  • stress, physiological
  • transcription factor RelA
  • tumor necrosis factor-alpha

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    de Roos, B., Rungapamestry, V., Ross, K., Rucklidge, G., Reid, M., Duncan, G., Horgan, G., Toomey, S., Browne, J., Loscher, C. E., Mills, K. H. G., & Roche, H. M. (2009). Attenuation of inflammation and cellular stress-related pathways maintains insulin sensitivity in obese type I interleukin-1 receptor knockout mice on a high-fat diet. Proteomics, 9(12), 3244-3256. https://doi.org/10.1002/pmic.200800761