Title |
Heme Oxygenase-1 Drives Metaflammation and Insulin Resistance in Mouse and Man
|
---|---|
Published in |
Cell, July 2014
|
DOI | 10.1016/j.cell.2014.04.043 |
Pubmed ID | |
Authors |
Alexander Jais, Elisa Einwallner, Omar Sharif, Klaus Gossens, Tess Tsai-Hsiu Lu, Selma M. Soyal, David Medgyesi, Daniel Neureiter, Jamile Paier-Pourani, Kevin Dalgaard, J. Catharina Duvigneau, Josefine Lindroos-Christensen, Thea-Christin Zapf, Sabine Amann, Simona Saluzzo, Florian Jantscher, Patricia Stiedl, Jelena Todoric, Rui Martins, Hannes Oberkofler, Simone Müller, Cornelia Hauser-Kronberger, Lukas Kenner, Emilio Casanova, Hedwig Sutterlüty-Fall, Martin Bilban, Karl Miller, Andrey V. Kozlov, Franz Krempler, Sylvia Knapp, Carey N. Lumeng, Wolfgang Patsch, Oswald Wagner, J. Andrew Pospisilik, Harald Esterbauer |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Austria | 2 | 8% |
United States | 2 | 8% |
Nepal | 2 | 8% |
Germany | 1 | 4% |
India | 1 | 4% |
United Kingdom | 1 | 4% |
Brazil | 1 | 4% |
Venezuela, Bolivarian Republic of | 1 | 4% |
Netherlands | 1 | 4% |
Other | 0 | 0% |
Unknown | 13 | 52% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 14 | 56% |
Scientists | 8 | 32% |
Practitioners (doctors, other healthcare professionals) | 2 | 8% |
Science communicators (journalists, bloggers, editors) | 1 | 4% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Germany | 4 | 1% |
United States | 3 | <1% |
United Kingdom | 3 | <1% |
Denmark | 2 | <1% |
Switzerland | 1 | <1% |
Portugal | 1 | <1% |
India | 1 | <1% |
Brazil | 1 | <1% |
Norway | 1 | <1% |
Other | 4 | 1% |
Unknown | 360 | 94% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 82 | 22% |
Researcher | 80 | 21% |
Student > Master | 38 | 10% |
Student > Bachelor | 29 | 8% |
Professor | 24 | 6% |
Other | 83 | 22% |
Unknown | 45 | 12% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 119 | 31% |
Medicine and Dentistry | 70 | 18% |
Biochemistry, Genetics and Molecular Biology | 63 | 17% |
Immunology and Microbiology | 19 | 5% |
Nursing and Health Professions | 9 | 2% |
Other | 39 | 10% |
Unknown | 62 | 16% |