Melatonin attenuated adipogenesis through reduction of the CCAAT/enhancer binding protein beta by regulating the glycogen synthase 3 beta in human mesenchymal stem cells
J. physiol. biochem
; 72(2): 145-155, jun. 2016. graf, ilus
Article
in English
| IBECS
| ID: ibc-168262
Responsible library:
ES1.1
Localization: BNCS
ABSTRACT
Adipogenic differentiation is characterized by an increase in two major transcription factors peroxisome proliferator-activated receptor gamma (PPARγ) and the CCAAT/enhancer binding protein alpha (C/EBPα). These two signals are influenced by C/EBPβ and C/EBPδ and cross-regulate each others expression during the initial stages of adipogenesis. Melatonin has been known to act as not only a direct scavenger of free radicals but also an inhibitor of glycogen synthase kinase 3β (GSK-3β). Here, we report that melatonin inhibits the adipogenic differentiation of human mesenchymal stem cells (hMSCs) which is due to the regulations of C/EBPβ in the early stage of adipogenic differentiation. Melatonin reduced the lipid accumulation, adiponectin, and lipoprotein lipase (LPL) during the adipogenic differentiation of hMSCs. Since C/EBPβ has been associated with the activation of PPARγ and the consensus site of ERK/GSK-3β, PPARγ and β-catenin were detected by immunofluorescence staining after pretreatment of melatonin. Melatonin blocked the activation of PPARγ which induced the degradation of β-catenin. Melatonin also decreased the levels of cyclic adenosine-3,5-monophosphate (cAMP) and reactive oxygen species (ROS). The cAMP triggered the activity of C/EBPβ which is a critical inducer of PPARγ and C/EBPα activation in the early stage of adipogenic differentiation, and this is further affected by ROS production. The adipogenic marker proteins such as PPARγ, C/EBPα, C/EBPβ, and pERK were also decreased by melatonin. In summary, melatonin inhibited the cAMP synthesis through ROS reduction and the phosphorylation of the ERK/GSK-3β site which is known to be responsible for C/EBPβ activation for adipogenic differentiation in hMSCs (AU)
RESUMEN
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Collection:
National databases
/
Spain
Database:
IBECS
Main subject:
Down-Regulation
/
Adipocytes
/
CCAAT-Enhancer-Binding Protein-beta
/
Adipogenesis
/
Mesenchymal Stem Cells
/
Glycogen Synthase Kinase 3 beta
/
Melatonin
Limits:
Humans
Language:
English
Journal:
J. physiol. biochem
Year:
2016
Document type:
Article
Institution/Affiliation country:
Dankook University/Korea