Anti-adipogenic effect and mechanism in 3T3-L1 preadipocytes by cyclosporin A, an immunosuppressant

Tae-Yun LeeYu-Kyoung ParkByeong-Churl Jang
Dept. of Molecular Medicine (분자의학)
Issue Date
Quantitative Bio-Science, Vol.37(1) : 57-63, 2018
Adipogenesis, also called the differentiation of preadipocytes, leads to the phenotype of mature adipocytes. However, excessive adipogenesis is closely linked to the development of obesity. Cyclosporin A, a neutral lipophilic cyclic undecapeptide isolated from the fungus Hypocladium inflatum gams, is known for several biological activities, including immunosuppression and anti-inflammation. Little is known about the relationship between cyclosporin A and obesity. In this study, we investigated the effect of cyclosporin A on adipogenesis in 3T3-L1 murine preadipocytes. 3T3-L1 preadipocyte differentiation was evaluated by Oil Red O staining and AdipoRed assay. The expression and phosphorylation levels of adipogenesis-related proteins in differentiating 3T3-L1 cells were evaluated by Western blotting. The mRNA expression levels of adipogenesis-related proteins in differentiating 3T3-L1 cells were measured by RT-PCR. Cyclosporin A considerably inhibited lipid accumulation and reduced triglyceride (TG) contents during the differentiation of 3T3-L1 preadipocytes into adipocytes in a concentration-dependent manner, suggesting its anti-adipogenic effect. Treatment with cyclosporin A at the concentrations tested was not cytotoxic to 3T3-L1 cells. Mechanistically, at a 10 μM concentration, cyclosporin A strongly down-regulated the protein and mRNA expressions of two adipogenic transcription factors, CCAAT/enhancer-binding protein-α (C/EBP-α) and peroxisome proliferator-activated receptor-γ (PPAR-γ) in differentiating 3T3-L1 cells. Furthermore, at a 10 μM concentration, cyclosporin A reduced the phosphorylation levels of signal transducers and activator of transcription-3 (STAT-3), other adipogenic transcription factor, and suppressed the protein and mRNA expressions of perilipin A, a protein that binds to and stabilizes lipid droplets, in differentiating 3T3-L1 cells. However, treatment with 10 μM of cyclosporin A did not modulate the protein and mRNA expressions of fatty acid synthase during 3T3-L1 preadipocyte differentiation. Collectively, these results show that cyclosporin A inhibits adipogenesis in differentiating 3T3-L1 cells, and that this inhibition is mediated through the reduced expression and phosphorylation levels of C/EBP-α, PPAR-γ, perilipin A, and STAT-3.
Cyclosporin AAdipogenesisC/EBP-αPPAR-γ3T3-L1
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