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Identification of Dacinostat as a potential anti-obesity compound through transcriptional activation of adipose thermogenesis in mice.
Chu, Xin Yi; Zhang, Cong Cong; Zhang, Rui Xin; Zhang, Jian Feng; Xia, Bo; Wu, Jiang Wei.
Afiliación
  • Chu XY; Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
  • Zhang CC; Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
  • Zhang RX; Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
  • Zhang JF; Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
  • Xia B; Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
  • Wu JW; Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address: wujiangwei@nwafu.edu.cn.
Biochim Biophys Acta Mol Basis Dis ; 1867(9): 166169, 2021 09 01.
Article en En | MEDLINE | ID: mdl-34000373
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tejido Adiposo Pardo / Activación Transcripcional / Fármacos Antiobesidad / Termogénesis / Tejido Adiposo Blanco / Obesidad Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Animals Idioma: En Revista: Biochim Biophys Acta Mol Basis Dis Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tejido Adiposo Pardo / Activación Transcripcional / Fármacos Antiobesidad / Termogénesis / Tejido Adiposo Blanco / Obesidad Tipo de estudio: Diagnostic_studies / Prognostic_studies Límite: Animals Idioma: En Revista: Biochim Biophys Acta Mol Basis Dis Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos