| RRC ID |
53812
|
| Author |
Mitani T, Watanabe S, Yoshioka Y, Katayama S, Nakamura S, Ashida H.
|
| Title |
Theobromine suppresses adipogenesis through enhancement of CCAAT-enhancer-binding protein β degradation by adenosine receptor A1.
|
| Journal |
Biochim Biophys Acta Mol Cell Res
|
| Abstract |
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 (4week-old) were administered with theobromine (0.1g/kg) for 7days. 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/EBPβ 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/EBPβ degradation. Theobromine increased sumoylation of C/EBPβ 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/EBPβ degradation by increasing its sumoylation. Furthermore, the inhibition of AR1 signaling is important for theobromine-induced C/EBPβ degradation.
|
| Volume |
1864(12)
|
| Pages |
2438-2448
|
| Published |
2017-12-1
|
| DOI |
10.1016/j.bbamcr.2017.09.017
|
| PII |
S0167-4889(17)30264-1
|
| PMID |
28965824
|
| MeSH |
3T3-L1 Cells
Adipocytes / metabolism
Adipogenesis / drug effects
Adipogenesis / genetics*
Animals
CCAAT-Enhancer-Binding Protein-beta / metabolism*
Cell Differentiation / genetics
Cysteine Endopeptidases / genetics*
Cysteine Endopeptidases / metabolism
Mice
Proteolysis / drug effects
Receptors, Purinergic P1 / genetics*
Signal Transduction
Sumoylation / genetics
Theobromine / administration & dosage
|
| IF |
4.739
|
| Times Cited |
7
|
| Resource |
| DNA material |
p3xFLAG-C/EBP beta (WT) (RDB15962)
p3xFLAG-C/EBP beta (K133R) (RDB15963) |
