Melatonin attenuated adipogenesis through reduction of the CCAAT/enhancer binding protein beta by regulating the glycogen synthase 3 beta in human mesenchymal stem cells

作者：Rhee Yun Hee; Ahn Jin Chul^*

来源：Journal of Physiology and Biochemistry, 2016, 72(2): 145-155.

DOI：10.1007/s13105-015-0463-3

• Adipogenesis
• hMSC
• Melatonin
• C/EBP beta
• ROS
• GSK3 beta/ERK

Adipogenic differentiation is characterized by an increase in two major transcription factors: peroxisome proliferator-activated receptor gamma (PPAR gamma) and the CCAAT/enhancer binding protein alpha (C/EBP alpha). These two signals are influenced by C/EBP beta and C/EBP delta and cross-regulate each other's 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 3 beta (GSK-3 beta). Here, we report that melatonin inhibits the adipogenic differentiation of human mesenchymal stem cells (hMSCs) which is due to the regulations of C/EBP beta 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/EBP beta has been associated with the activation of PPAR gamma and the consensus site of ERK/GSK-3 beta, PPAR gamma and beta-catenin were detected by immunofluorescence staining after pretreatment of melatonin. Melatonin blocked the activation of PPAR gamma which induced the degradation of beta-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/EBP beta which is a critical inducer of PPAR gamma and C/EBP alpha activation in the early stage of adipogenic differentiation, and this is further affected by ROS production. The adipogenic marker proteins such as PPAR gamma, C/EBP alpha, C/EBP beta, and pERK were also decreased by melatonin. In summary, melatonin inhibited the cAMP synthesis through ROS reduction and the phosphorylation of the ERK/GSK-3 beta site which is known to be responsible for C/EBP beta activation for adipogenic differentiation in hMSCs.

• 出版日期2016-6