@article{oai:soar-ir.repo.nii.ac.jp:00020858,
 author = {Mitani, Takakazu and Watanabe, Shun and Yoshioka, Yasukiyo and Katayama, Shigeru and Nakamura, Soichiro and Ashida, Hitoshi},
 issue = {12},
 journal = {BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH},
 month = {Dec},
 note = {Theobromine, a methylxanthine derived from cacao beans, reportedly has various health-promoting properties but molecular mechanism by which effects of theobromine on adipocyte differentiation and adipogenesis remains unclear. In this study, we aimed to clarify the molecular mechanisms of the anti-adipogenic effect of theobromine in vitro and in vivo. ICR mice (4 week-old) were administered with theobromine (0.1 g/kg) for 7 days. Theobromine administration attenuated gains in body and epididymal adipose tissue weights in mice and suppressed expression of adipogenic-associated genes in mouse adipose tissue. In 3T3-L1 preadipocytes, theobromine caused degradation of C/EBP beta protein by the ubiquitin-proteasome pathway. Pull down assay showed that theobromine selectively interacts with adenosine receptor A1(AR1), and AR1 knockdown inhibited theobromine-induced C/ESPfi degradation. Theobromine increased sumoylation of C/EBP beta' at Lys133. Expression of the small ubiquitin-like modifier (SUMO)-specific protease 2 (SENP2) gene, coding for a desumoylation enzyme, was suppressed by theobromine. In vivo knockdown studies showed that AR1 knockdown in mice attenuated the anti-adipogenic effects of theobromine in younger mice. Theobromine suppresses adipocyte differentiation and induced C/EBPP degradation by increasing its sumoylation. Furthermore, the inhibition of AR1 signaling is important for theobromine-induced C/EBP beta degradation., Article, BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH.1864(12):2438-2448(2017)},
 pages = {2438--2448},
 title = {Theobromine suppresses adipogenesis through enhancement of CCAAT-enhancer-binding protein beta degradation by adenosine receptor A1},
 volume = {1864},
 year = {2017}
}