| First Author | Hernandez ED | Year | 2014 |
| Journal | Cell Metab | Volume | 20 |
| Issue | 3 | Pages | 499-511 |
| PubMed ID | 25043814 | Mgi Jnum | J:215606 |
| Mgi Id | MGI:5605904 | Doi | 10.1016/j.cmet.2014.06.008 |
| Citation | Hernandez ED, et al. (2014) A macrophage NBR1-MEKK3 complex triggers JNK-mediated adipose tissue inflammation in obesity. Cell Metab 20(3):499-511 |
| abstractText | The c-Jun NH(2)-terminal kinase (JNK) is a critical determinant of obesity-associated inflammation and glucose intolerance. The upstream mechanisms controlling this pathway are still unknown. Here we report that the levels of the PB1 domain-containing adaptor NBR1 correlated with the expression of proinflammatory molecules in adipose tissue from human patients with metabolic syndrome, suggesting that NBR1 plays a key role in adipose-tissue inflammation. We also show that NBR1 inactivation in the myeloid compartment impairs the function, M1 polarization, and chemotactic activity of macrophages; prevents inflammation of adipose tissue; and improves glucose tolerance in obese mice. Furthermore, we demonstrate that an interaction between the PB1 domains of NBR1 and the mitogen-activated kinase kinase 3 (MEKK3) enables the formation of a signaling complex required for the activation of JNK. Together, these discoveries identify an NBR1-MEKK3 complex as a key regulator of JNK signaling and adipose tissue inflammation in obesity. |
