Abstract
Aim: Our previously reported naphthofuran derivative BF4, identified as a potent silent information regulator 1 (SIRT1) activator, could alleviate high glucose stimulating apoptosis and inflammation response in human renal tubular epithelial (HK-2) cells.
Introduction: In this study, the underlying effects of BF4 on lipid metabolism in 3T3-L1 adipocytes were investigated.
Methods: The effects of BF4 on pre-adipocyte differentiation and adipocyte lipolysis were studied using oil red O staining and quantitative glycerol and triglyceride content assay kits. Moreover, the molecular mechanism of BF4 on adipogenesis and lipid metabolism in 3T3-L1 adipocytes was investigated by real-time quantitative PCR and Western blotting analysis.
Results: We found that compound BF4 significantly decreased adipogenesis and lipid accumulation and inhibited the differentiation of 3T3-L1 pre-adipocytes into adipocytes. Moreover, compound BF4 decreased the expressions of several key regulators in adipocyte differentiation, including C/EBPβ and PPARγ, and their downstream lipogenesis targets via the activation of the SIRT1/ AMPK pathway.
Conclusion: Our results demonstrated that the novel SIRT1 activator BF4 might be a potent candidate for regulating lipid metabolism.
Graphical Abstract
[http://dx.doi.org/10.1016/j.cmet.2011.10.003] [PMID: 22055498]
[http://dx.doi.org/10.1038/s41430-018-0100-7] [PMID: 29535406]
[http://dx.doi.org/10.1074/jbc.272.2.971] [PMID: 8995390]
[http://dx.doi.org/10.1016/S1471-4914(02)02396-1] [PMID: 12223316]
[http://dx.doi.org/10.1371/journal.pcbi.1000324] [PMID: 19325873]
[http://dx.doi.org/10.1006/bbrc.1999.0897] [PMID: 10381378]
[http://dx.doi.org/10.1101/gad.1467506] [PMID: 17079682]
[http://dx.doi.org/10.1371/journal.ppat.1008319] [PMID: 32106265]
[http://dx.doi.org/10.1126/science.1099196] [PMID: 15205477]
[http://dx.doi.org/10.1038/nrm.2016.93] [PMID: 27552971]
[http://dx.doi.org/10.1016/j.tips.2013.12.004] [PMID: 24439680]
[http://dx.doi.org/10.1016/j.cell.2006.11.013] [PMID: 17112576]
[http://dx.doi.org/10.1038/nature05354] [PMID: 17086191]
[http://dx.doi.org/10.1038/nature06261] [PMID: 18046409]
[http://dx.doi.org/10.1371/journal.pone.0142081] [PMID: 26556603]
[http://dx.doi.org/10.3389/fphar.2021.653233] [PMID: 33995069]
[http://dx.doi.org/10.3390/molecules24101894] [PMID: 31108834]
[http://dx.doi.org/10.1002/mnfr.201100772] [PMID: 22945685]
[http://dx.doi.org/10.3390/nu10111734] [PMID: 30424495]
[http://dx.doi.org/10.1006/meth.2001.1262] [PMID: 11846609]
[http://dx.doi.org/10.18632/oncotarget.18630] [PMID: 29088765]
[http://dx.doi.org/10.1080/14756366.2017.1344979] [PMID: 28718674]