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A novel peptide suppresses adipogenic differentiation through activation of the AMPK pathway

Author:
Shen, Dan, Li, Yun, Wang, Xing, Wang, Fei, Huang, Fangyan, Cao, Yan, You, Lianghui, wen, Juan, Wang, Yan, Cui, Xianwei, Ji, Chenbo, Guo, Xirong
Source:
Biochemical and biophysical research communications 2019 v.510 no.3 pp. 395-402
ISSN:
0006-291X
Subject:
adipogenesis, anti-obesity agents, apoptosis, binding proteins, cell cycle, gene expression, humans, lipids, mice, noninsulin-dependent diabetes mellitus, obesity, peroxisome proliferator-activated receptor gamma, protein kinases, public health, stem cells
Abstract:
Obesity rates have risen rapidly over the past several decades and obesity is now a global public health challenge. The reduction of excessive adipogenesis is thought to be an effective intervention for obesity and obesity-related metabolic diseases such as type 2 diabetes. In this study, a novel peptide PDBSN was identified that functions to suppress adipogenesis. In both human preadipocytes and mouse adipose-derived stem cells (ADSCs), PDBSN exhibited a suppressive effect on the accumulation of lipids and the expression of genes as well as their corresponding proteins (CCAAT/enhancer binding protein (C/EBP)β, C/EBPα and nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ)) relevant to adipogenic cell differentiation. Although adipogenesis decreased, the preadipocyte number and proliferation were not influenced by the PDBSN treatment. Apoptosis and the cell cycle were also determined to not have a role in the action of PDBSN. Mechanistically, the activity of the AMPK (adenosine 5ʹ-monophosphate-activated protein kinase) pathway was markedly increased upon PDBSN treatment. Moreover, treatment of preadipocytes with compound C, a selective AMPK inhibitor, abolished the effect of PDBSN in anti-adipogenesis, suggesting that the function of PDBSN relied on the AMPK pathway. These results suggest an effective role for PDBSN in suppressing adipogenesis and show potential for anti-obesity drug discovery.
Agid:
6280712