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Selected Publication:

Type of publication: Journal Article
Type of document: Full Paper

Year: 2014

Authors: 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

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

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



Authors Vetmeduni Vienna:

Duvigneau Catharina
Kenner Lukas
Müller Simone

Vetmed Research Units
Institute for Medical Biochemistry
Institute of Pathology, Pathology of Laboratory Animals
Institute of Animal Breeding and Genetics, Unit of Molecular Genetics


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


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