Identification of Dacinostat as a potential anti-obesity compound through transcriptional activation of adipose thermogenesis in mice.
Biochim Biophys Acta Mol Basis Dis
; 1867(9): 166169, 2021 09 01.
Article
in En
| MEDLINE
| ID: mdl-34000373
ABSTRACT
Obesity is a worldwide health problem. Activating fat mobilization and reducing fat synthesis is a promising strategy to mitigate obesity and its complicated metabolic diseases. However, few clinically effective and safe agents conform to the strategy. In the present study, by screening the next-generation L1000-based CMAP small molecule library, we identify histone deacetylase inhibitor Dacinostat, which has been previously tested in clinical trials for patients with advanced solid tumors, as an anti-obesity candidate. Administration of Dacinostat prevents high-fat diet-induced obesity, insulin resistance, and fatty liver in mice without causing adverse effects. Dacinostat treatment enhances adipose thermogenesis as shown by elevated body temperature, accompanied with high mRNA expression of Ucp1 and Ppargc1α. Mechanistically, we show that the thermogenic effect of Dacinostat is achieved by acetylation of histone 3 lysine 27 mediated transcriptional activation of Ucp1 and Ppargc1α in adipose tissue. In conclusion, these findings suggest that Dacinostat is a potential anti-obesity compound through transcriptional activation of adipose thermogenesis.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Adipose Tissue, Brown
/
Transcriptional Activation
/
Anti-Obesity Agents
/
Thermogenesis
/
Adipose Tissue, White
/
Obesity
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Biochim Biophys Acta Mol Basis Dis
Year:
2021
Document type:
Article
Affiliation country:
China