| First Author | Lee DK | Year | 2022 |
| Journal | Nat Commun | Volume | 13 |
| Issue | 1 | Pages | 6303 |
| PubMed ID | 36272977 | Mgi Jnum | J:330638 |
| Mgi Id | MGI:7379630 | Doi | 10.1038/s41467-022-34110-1 |
| Citation | Lee DK, et al. (2022) REDD1 promotes obesity-induced metabolic dysfunction via atypical NF-kappaB activation. Nat Commun 13(1):6303 |
| abstractText | Regulated in development and DNA damage response 1 (REDD1) expression is upregulated in response to metabolic imbalance and obesity. However, its role in obesity-associated complications is unclear. Here, we demonstrate that the REDD1-NF-kappaB axis is crucial for metabolic inflammation and dysregulation. Mice lacking Redd1 in the whole body or adipocytes exhibited restrained diet-induced obesity, inflammation, insulin resistance, and hepatic steatosis. Myeloid Redd1-deficient mice showed similar results, without restrained obesity and hepatic steatosis. Redd1-deficient adipose-derived stem cells lost their potential to differentiate into adipocytes; however, REDD1 overexpression stimulated preadipocyte differentiation and proinflammatory cytokine expression through atypical IKK-independent NF-kappaB activation by sequestering IkappaBalpha from the NF-kappaB/IkappaBalpha complex. REDD1 with mutated Lys(219/220)Ala, key amino acid residues for IkappaBalpha binding, could not stimulate NF-kappaB activation, adipogenesis, and inflammation in vitro and prevented obesity-related phenotypes in knock-in mice. The REDD1-atypical NF-kappaB activation axis is a therapeutic target for obesity, meta-inflammation, and metabolic complications. |
