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
DNA material p3xFLAG-C/EBP beta (WT) (RDB15962) p3xFLAG-C/EBP beta (K133R) (RDB15963)