1. Heme Oxygenase-1 Drives Metaflammation and Insulin Resistance in Mouse and Man.
- Author
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Jais, Alexander, Einwallner, Elisa, Omar Sharif, Klaus Gossens, Tess Tsai-Hsiu Lu, Soyal, Selma M., Medgyesi, David, Neureiter, Daniel, Paier-Pourani, Jamile, Dalgaard, Kevin, Duvigneau, J. Catharina, Lindroos-Christensen, Josefine, Zapf, Thea-Christin, Amann, Sabine, Saluzzo, Simona, Jantscher, Florian, Stiedl, Patricia, Todoric, Jelena, Martins, Rui, and Oberkofler, Hannes
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HEME oxygenase , *INSULIN resistance , *OBESITY , *DIABETES , *METABOLIC disorders , *LIVER cells , *MACROPHAGES , *FATTY degeneration - 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-KB amplification in macrophages and for insulin signaling in hepatocytes. These findings identify HO-1 inhibition as a potential therapeutic strategy for metabolic disease. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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