Veterinärmedizinische Universität Wien Forschungsinformationssystem VetDoc

Grafischer Link zur Startseite der Vetmeduni Vienna

Gewählte Publikation:

Publikationstyp: Zeitschriftenaufsatz
Dokumenttyp: Originalarbeit

Jahr: 2014

AutorInnen: Jais, A; Einwallner, E; Sharif, O; Gossens, K; Lu, TT; Soyal, SM; Medgyesi, D; Neureiter, D; Paier-Pourani, J; Dalgaard, K; Duvigneau, JC; Lindroos-Christensen, J; Zapf, TC; Amann, S; Saluzzo, S; Jantscher, F; Stiedl, P; Todoric, J; Martins, R; Oberkofler, H; Müller, S; Hauser-Kronberger, C; Kenner, L; Casanova, E; Sutterlüty-Fall, H; Bilban, M; Miller, K; Kozlov, AV; Krempler, F; Knapp, S; Lumeng, CN; Patsch, W; Wagner, O; Pospisilik, JA; Esterbauer, H

Titel: Heme oxygenase-1 drives metaflammation and insulin resistance in mouse and man.

Quelle: Cell. 2014; 158(1):25-40



Autor/innen der Vetmeduni Vienna:

Duvigneau Catharina
Kenner Lukas
Müller Simone

Beteiligte Vetmed-Organisationseinheiten
Institut für Pathologie, Abteilung für Labortierpathologie
Institut für Tierzucht und Genetik, Abteilung für Molekulare Genetik
Institut für Medizinische Biochemie


Abstract:
Obesity and diabetes affect more than half a billion individuals worldwide. Interestingly, the two conditions do not always coincide and the molecular determinants of "healthy" versus "unhealthy" obesity remain ill-defined. Chronic metabolic inflammation (metaflammation) is believed to be pivotal. Here, we tested a hypothesized anti-inflammatory role for heme oxygenase-1 (HO-1) in the development of metabolic disease. Surprisingly, in matched biopsies from "healthy" versus insulin-resistant obese subjects we find HO-1 to be among the strongest positive predictors of metabolic disease in humans. We find that hepatocyte and macrophage conditional HO-1 deletion in mice evokes resistance to diet-induced insulin resistance and inflammation, dramatically reducing secondary disease such as steatosis and liver toxicity. Intriguingly, cellular assays show that HO-1 defines prestimulation thresholds for inflammatory skewing and NF-κB amplification in macrophages and for insulin signaling in hepatocytes. These findings identify HO-1 inhibition as a potential therapeutic strategy for metabolic disease.

Keywords Pubmed: Adipose Tissue/metabolism
Animals
Diet, High-Fat
Heme Oxygenase-1/metabolism*
Hepatocytes/metabolism
Humans
Inflammation/metabolism
Insulin Resistance*
Liver/metabolism
Macrophages/metabolism
Membrane Proteins/metabolism*
Metabolic Diseases/metabolism
Metabolic Diseases/physiopathology
Mice
Mice, Knockout
Obesity/complications*
Obesity/physiopathology
Reactive Oxygen Species/metabolism


© Veterinärmedizinische Universität Wien Hilfe und DownloadsErklärung zur Barrierefreiheit