Adipocytes from New Zealand obese mice exhibit aberrant proinflammatory reactivity to the stress signal heat shock protein 60

J Diabetes Res. 2014;2014:187153. doi: 10.1155/2014/187153. Epub 2014 Feb 5.

Abstract

Adipocytes release immune mediators that contribute to diabetes-associated inflammatory processes. As the stress protein heat shock protein 60 (Hsp60) induces proinflammatory adipocyte activities, we hypothesized that adipocytes of diabetes-predisposed mice exhibit an increased proinflammatory reactivity to Hsp60. Preadipocytes and mature adipocytes from nonobese diabetic (NOD), New Zealand obese (NZO), and C57BL/6J mice were analyzed for Hsp60 binding, Hsp60-activated signaling pathways, and Hsp60-induced release of the chemokine CXCL-1 (KC), interleukin 6 (IL-6), and macrophage chemoattractant protein-1 (MCP-1). Hsp60 showed specific binding to (pre-)adipocytes of NOD, NZO, and C57BL/6J mice. Hsp60 binding involved conserved binding structure(s) and Hsp60 epitopes and was strongest to NZO mouse-derived mature adipocytes. Hsp60 exposure induced KC, IL-6, and MCP-1 release from (pre-)adipocytes of all mouse strains with a pronounced increase of IL-6 release from NZO mouse-derived adipocytes. Compared to NOD and C57BL/6J mouse derived cells, Hsp60-induced formation of IL-6, KC, and MCP-1 from NZO mouse-derived (pre-)adipocytes strongly depended on NF κ B-activation. Increased Hsp60 binding and Hsp60-induced IL-6 release by mature adipocytes of NZO mice suggest that enhanced adipocyte reactivity to the stress signal Hsp60 contributes to inflammatory processes underlying diabetes associated with obesity and insulin resistance.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / immunology
  • Adipocytes / metabolism*
  • Adipocytes / pathology
  • Adipogenesis
  • Animals
  • Cells, Cultured
  • Chaperonin 60 / genetics
  • Chaperonin 60 / metabolism*
  • Chemokine CCL2 / agonists
  • Chemokine CCL2 / biosynthesis
  • Chemokine CCL2 / metabolism
  • Chemokine CXCL1 / agonists
  • Chemokine CXCL1 / biosynthesis
  • Chemokine CXCL1 / metabolism
  • Cytokines / agonists
  • Cytokines / biosynthesis
  • Cytokines / metabolism*
  • Female
  • Interleukin-6 / agonists
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / metabolism
  • Intra-Abdominal Fat / immunology
  • Intra-Abdominal Fat / metabolism
  • Intra-Abdominal Fat / pathology
  • MAP Kinase Signaling System*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Mice, Obese
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • NF-kappa B / agonists
  • NF-kappa B / metabolism
  • Obesity / immunology
  • Obesity / metabolism*
  • Obesity / pathology
  • Panniculitis / immunology
  • Panniculitis / metabolism*
  • Panniculitis / pathology
  • Recombinant Proteins / metabolism
  • Up-Regulation*

Substances

  • Ccl2 protein, mouse
  • Chaperonin 60
  • Chemokine CCL2
  • Chemokine CXCL1
  • Cxcl1 protein, mouse
  • Cytokines
  • HSPD1 protein, human
  • Interleukin-6
  • Mitochondrial Proteins
  • NF-kappa B
  • Recombinant Proteins
  • interleukin-6, mouse