2024-03-29T11:44:10Z
https://soar-ir.repo.nii.ac.jp/oai
oai:soar-ir.repo.nii.ac.jp:00020858
2022-12-14T04:18:12Z
1016:1017
Theobromine suppresses adipogenesis through enhancement of CCAAT-enhancer-binding protein beta degradation by adenosine receptor A1
Mitani, Takakazu
Watanabe, Shun
Yoshioka, Yasukiyo
Katayama, Shigeru
Nakamura, Soichiro
Ashida, Hitoshi
Adenosine receptor
Adipogenesis
CCAAT/enhancer-binding protein
Sumoylation
Theobromine
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)
journal article
ELSEVIER SCIENCE BV
2017-12
application/pdf
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
12
1864
2438
2448
0167-4889
AA1050609X
https://soar-ir.repo.nii.ac.jp/record/20858/files/16K18701_02.pdf
eng
28965824
https://pubmed.ncbi.nlm.nih.gov/28965824/
10.1016/j.bbamcr.2017.09.017
https://doi.org/10.1016/j.bbamcr.2017.09.017
© 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/