Cathepsin K null mice show reduced adiposity during the rapid accumulation of fat stores

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Funicello, M., Novelli, M., Ragni, M., Vottari, T., Cocuzza, C., Soriano-Lopez, J., Chiellini, C., Boschi, F., Marzola, P., Masiello, P., Saftig, P., Santini, F., St-Jacques, R., Desmarais, S., Morin, N., Mancini, J., Percival, M.D., Pinchera, A., Maffei, M.

  • PLoS ONE
  • 2007
  • 3.041
  • 361(1):140-5.
  • Canine,Human,Mouse,Non-Human Primate,Rat
  • MSD
  • Plasma
  • 免疫/内分泌
  • 肥胖
  • Insulin, Leptin




The contribution of nutrient overload and associated inflammation to insulin resistance has highlighted several therapeutic targets including c-Jun N-terminal kinase (JNK) and S6 kinase (S6K). To investigate how a lipopolysaccharide (LPS)-mediated inflammatory response may modulate pathways implicated in insulin resistance, we characterized the LPS-induced changes in key biomarkers. Administration of 0.06-4 mg/kg LPS to C57BL/6 mice stimulated increases in plasma levels of TNFalpha, IL-12p40, IL-6 and MCP-1 and in JNK activity as measured by phosphorylated c-Jun in fat. For the first time, we show that LPS induces S6K activity by up to 6.1-fold, as measured by the phosphorylation of S6 ribosomal protein in liver, and increases by up to 1.8-fold, plasma levels of the novel pro-inflammatory cytokine osteopontin which is implicated in the pathogenesis of insulin resistance. These novel findings suggest that LPS administration may form the basis of an acute in vivo pharmacodynamic model for therapies targeting multiple pathways implicated in insulin resistance.
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