| First Author | Lopez-Alcantara N | Year | 2023 |
| Journal | iScience | Volume | 26 |
| Issue | 10 | Pages | 108064 |
| PubMed ID | 37822510 | Mgi Jnum | J:341734 |
| Mgi Id | MGI:7540195 | Doi | 10.1016/j.isci.2023.108064 |
| Citation | Lopez-Alcantara N, et al. (2023) Lack of thyroid hormone receptor beta is not detrimental for non-alcoholic steatohepatitis progression. iScience 26(10):108064 |
| abstractText | Agonists for thyroid hormone receptor beta (TRbeta) show promise in preclinical studies and clinical trials to improve non-alcoholic fatty liver disease. A recent study on human livers, however, revealed reduced TRbeta expression in non-alcoholic steatohepatitis (NASH), indicating a developing thyroid hormone resistance, which could constitute a major obstacle for those agonists. Using a rapid NASH paradigm combining choline-deficient high-fat diet and thermoneutrality, we confirm that TRbeta declines during disease progression in mice similar to humans. Contrary to expectations, mice lacking TRbeta showed less liver fibrosis, and NASH marker genes were not elevated. Conversely, increasing TRbeta expression in wild-type NASH mice using liver-targeted gene therapy did not improve histology, gene expression, or metabolic parameters, indicating that TRbeta receptor levels are of minor relevance for NASH development and progression in our model, and suggest that liver-rather than isoform-specificity might be more relevant for NASH treatment with thyroid hormone receptor agonists. |
