| First Author | Personnaz J | Year | 2022 |
| Journal | Sci Adv | Volume | 8 |
| Issue | 12 | Pages | eabg9055 |
| PubMed ID | 35333579 | Mgi Jnum | J:325579 |
| Mgi Id | MGI:7260966 | Doi | 10.1126/sciadv.abg9055 |
| Citation | Personnaz J, et al. (2022) Nuclear HMGB1 protects from nonalcoholic fatty liver disease through negative regulation of liver X receptor. Sci Adv 8(12):eabg9055 |
| abstractText | Dysregulations of lipid metabolism in the liver may trigger steatosis progression, leading to potentially severe clinical consequences such as nonalcoholic fatty liver diseases (NAFLDs). Molecular mechanisms underlying liver lipogenesis are very complex and fine-tuned by chromatin dynamics and multiple key transcription factors. Here, we demonstrate that the nuclear factor HMGB1 acts as a strong repressor of liver lipogenesis. Mice with liver-specific Hmgb1 deficiency display exacerbated liver steatosis, while Hmgb1-overexpressing mice exhibited a protection from fatty liver progression when subjected to nutritional stress. Global transcriptome and functional analysis revealed that the deletion of Hmgb1 gene enhances LXRalpha and PPARgamma activity. HMGB1 repression is not mediated through nucleosome landscape reorganization but rather via a preferential DNA occupation in a region carrying genes regulated by LXRalpha and PPARgamma. Together, these findings suggest that hepatocellular HMGB1 protects from liver steatosis development. HMGB1 may constitute a new attractive option to therapeutically target the LXRalpha-PPARgamma axis during NAFLD. |
