Inhibition of lipid droplet formation by Ser/Thr protein phosphatase PPM1D inhibitor, SL-176

PloS One
Rui KamadaKazuyasu Sakaguchi

Abstract

Obesity is a worldwide public health problem, which is associated with various severe diseases including diabetes, hypertension, atherosclerosis, and cancer. Recent studies have revealed that combination treatment of several different compounds using low doses is effective to reduce side effects. Thus, there is a need to develop an efficient inhibitor for reducing lipid droplets with a divergent target/pathway. Ser/Thr protein phosphatase PPM1D is involved in cellular metabolic processes and is a promising target for anti-obesity treatment. We have previously developed a potent and specific PPM1D inhibitor, SL-176. In this study, we demonstrated that significant reduction of lipid droplet formation in adipocytes by the PPM1D specific inhibitor, SL-176. Using Oil-red O staining and fluorescent imaging of lipid droplet, we found that treatment of SL-176 significantly suppressed lipid droplet formation of 3T3-L1 cells both in amount and in size. SL-176 also repressed mRNA and protein expression of PPARγ and C/EBPα, adipogenic markers, at nontoxic conditions. Thus, SL-176 is a unique and potent inhibitor of lipid droplet formation that acts via PPM1D, a novel target toward inhibiting adipocyte differentiation.

References

Jun 10, 1997·Proceedings of the National Academy of Sciences of the United States of America·M FiscellaE Appella
May 23, 2008·The Journal of Nutritional Biochemistry·Srujana RayalamClifton A Baile
Aug 25, 2010·Phytochemistry·Jong Won Yun
Nov 15, 2011·Trends in Endocrinology and Metabolism : TEM·Rasmus SiersbækSusanne Mandrup
Nov 26, 2011·Bioorganic & Medicinal Chemistry Letters·Hiroaki YagiKazuyasu Sakaguchi
Feb 9, 2012·The Journal of Biological Chemistry·Margret PaarHeimo Wolinski
Jul 10, 2012·Cell Metabolism·Xavier Le GuezennecDmitry V Bulavin
May 22, 2013·Biochimica Et Biophysica Acta·Manige KonigeCarole Sztalryd
Feb 20, 2014·Journal of Natural Medicines·Chin Piow WongHiroshi Morita
Nov 8, 2014·Molecular Endocrinology·Heather L ArmataHayla K Sluss
Feb 24, 2015·Current Opinion in Cell Biology·Hayaa F Hashemi, Joel M Goodman
Sep 12, 2015·Bioorganic & Medicinal Chemistry·Sari OgasawaraKazuyasu Sakaguchi
Mar 8, 2016·The American Journal of Medicine·Homayoun L DaneschvarGerald W Smetana
Feb 10, 2017·Cellular and Molecular Life Sciences : CMLS·Dahu LiLingling Zhu

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Citations

Jul 11, 2020·Pharmacology & Therapeutics·Rui KamadaKazuyasu Sakaguchi

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Methods Mentioned

BETA
Assay
fluorescence microscopy
PCR

Software Mentioned

PowerPoint

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