| First Author | Jais A | Year | 2014 |
| Journal | Cell | Volume | 158 |
| Issue | 1 | Pages | 25-40 |
| PubMed ID | 24995976 | Mgi Jnum | J:214639 |
| Mgi Id | MGI:5603503 | Doi | 10.1016/j.cell.2014.04.043 |
| Citation | Jais A, et al. (2014) Heme oxygenase-1 drives metaflammation and insulin resistance in mouse and man. Cell 158(1):25-40 |
| abstractText | 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-kappaB amplification in macrophages and for insulin signaling in hepatocytes. These findings identify HO-1 inhibition as a potential therapeutic strategy for metabolic disease. |
