Inhibition of lipid droplet formation by Ser/Thr protein phosphatase PPM1D inhibitor, SL-176.
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. Th...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0212682 |
| _version_ | 1818572149813673984 |
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| author | Rui Kamada Nozomi Kimura Fumihiko Yoshimura Keiji Tanino Kazuyasu Sakaguchi |
| author_facet | Rui Kamada Nozomi Kimura Fumihiko Yoshimura Keiji Tanino Kazuyasu Sakaguchi |
| author_sort | Rui Kamada |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T18:53:27Z |
| format | Article |
| id | doaj.art-2dcb7aaa3b294d8c8aa59603568faa0d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T18:53:27Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-2dcb7aaa3b294d8c8aa59603568faa0d2022-12-21T22:51:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01142e021268210.1371/journal.pone.0212682Inhibition of lipid droplet formation by Ser/Thr protein phosphatase PPM1D inhibitor, SL-176.Rui KamadaNozomi KimuraFumihiko YoshimuraKeiji TaninoKazuyasu SakaguchiObesity 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.https://doi.org/10.1371/journal.pone.0212682 |
| spellingShingle | Rui Kamada Nozomi Kimura Fumihiko Yoshimura Keiji Tanino Kazuyasu Sakaguchi Inhibition of lipid droplet formation by Ser/Thr protein phosphatase PPM1D inhibitor, SL-176. PLoS ONE |
| title | Inhibition of lipid droplet formation by Ser/Thr protein phosphatase PPM1D inhibitor, SL-176. |
| title_full | Inhibition of lipid droplet formation by Ser/Thr protein phosphatase PPM1D inhibitor, SL-176. |
| title_fullStr | Inhibition of lipid droplet formation by Ser/Thr protein phosphatase PPM1D inhibitor, SL-176. |
| title_full_unstemmed | Inhibition of lipid droplet formation by Ser/Thr protein phosphatase PPM1D inhibitor, SL-176. |
| title_short | Inhibition of lipid droplet formation by Ser/Thr protein phosphatase PPM1D inhibitor, SL-176. |
| title_sort | inhibition of lipid droplet formation by ser thr protein phosphatase ppm1d inhibitor sl 176 |
| url | https://doi.org/10.1371/journal.pone.0212682 |
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