Adipocytes from New Zealand Obese Mice Exhibit Aberrant Proinflammatory Reactivity to the Stress Signal Heat Shock Protein 60

• Published in: Journal of diabetes research 2014-01, Vol.2014 (2014), p.1-13
• Main Authors: Burkart, Volker, Wohlrab, Ulrike, Kriebel, Jennifer, Märker, Tina, Habich, Christiane
• Format: Article
• Language: English
• Subjects: Adipocytes; Adipocytes - immunology; Adipocytes - metabolism; Adipocytes - pathology; Adipogenesis; Animals; Antibodies; 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; Chemokines; Cytokines; Cytokines - agonists; Cytokines - biosynthesis; Cytokines - metabolism; Diabetes; Female; Heat shock proteins; Insulin resistance; Interleukin-6 - agonists; Interleukin-6 - biosynthesis; Interleukin-6 - metabolism; Intra-Abdominal Fat - immunology; Intra-Abdominal Fat - metabolism; Intra-Abdominal Fat - pathology; Laboratory animals; Male; MAP Kinase Signaling System; 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; Statistical analysis; Up-Regulation
• ISSN: 2314-6745; 2314-6753
• DOI: 10.1155/2014/187153

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 NFκB-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.