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Theobromine suppresses adipogenesis through enhancement of CCAAT-enhancer-binding protein β degradation by adenosine receptor A1
- Source :
- Biochimica et biophysica acta. Molecular cell research. 1864(12)
- Publication Year :
- 2017
-
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.
- Subjects :
- 0301 basic medicine
SUMO protein
Adipose tissue
Biology
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Adipocyte
3T3-L1 Cells
medicine
Adipocytes
Animals
Molecular Biology
Theobromine
Gene knockdown
Adipogenesis
Ccaat-enhancer-binding proteins
CCAAT-Enhancer-Binding Protein-beta
Receptors, Purinergic P1
Sumoylation
Cell Differentiation
Cell Biology
Adenosine receptor
Cell biology
Cysteine Endopeptidases
030104 developmental biology
chemistry
Biochemistry
030220 oncology & carcinogenesis
Proteolysis
medicine.drug
Signal Transduction
Subjects
Details
- ISSN :
- 01674889
- Volume :
- 1864
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Biochimica et biophysica acta. Molecular cell research
- Accession number :
- edsair.doi.dedup.....466a394531941468ec764fb6a90aadfe