Heme Oxygenase-1 Drives Metaflammation and Insulin Resistance in Mouse and Man
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- Catégories : Domaines de recherche divers , Publications - ID: 643

Alexander Jais,Elisa Einwallner, Omar Sharif, Klaus Gossens et al.

Medical University of Vienna, Vienna, Austria


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-?B amplification in macrophages and for insulin signaling in hepatocytes. These findings identify HO-1 inhibition as a potential therapeutic strategy for metabolic disease.

BIOSEB Instruments Used:
OXYLET, Indirect Calorimeter (OXYLET)

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