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Lipid Droplet Formation Is Regulated by Ser/Thr Phosphatase PPM1D via Dephosphorylation of Perilipin 1

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Title: Lipid Droplet Formation Is Regulated by Ser/Thr Phosphatase PPM1D via Dephosphorylation of Perilipin 1
Authors: Kamada, Rui Browse this author
Uno, Sae Browse this author
Kimura, Nozomi Browse this author
Yoshimura, Fumihiko Browse this author
Tanino, Keiji Browse this author
Sakaguchi, Kazuyasu Browse this author →KAKEN DB
Keywords: phosphatase inhibitor
lipid droplet
dephosphorylation
adipocytes
Issue Date: 10-Oct-2022
Publisher: MDPI
Journal Title: International Journal of Molecular Sciences
Volume: 23
Issue: 19
Start Page: 12046
Publisher DOI: 10.3390/ijms231912046
Abstract: Hypertrophy and hyperplasia of white adipocytes induce obesity, leading to diseases such as type 2 diabetes and hypertension, and even cancer. Hypertrophy of white adipocytes is attributed to the excessive storage of the energy form of triglycerides in lipid droplets (LDs). LDs are fat storage organelles that maintain whole-body energy homeostasis. It is important to understand the mechanism of LD formation for the development of obesity therapy; however, the regulatory mechanisms of LD size and formation are not fully understood. In this study, we demonstrated that the PPM family phosphatase PPM1D regulates LD formation. PPM1D specific inhibitor, SL-176 significantly decreased LD formation via two different pathways: dependent of and independent of adipocyte-differentiation processes. In the mature white adipocytes after differentiation, LD formation was found to be controlled by PPM1D via dephosphorylation of Ser511 of perilipin 1. We found that inhibition of PPM1D in mature white adipocytes significantly reduced the size of the LDs via dephosphorylation of Ser511 of perilipin 1 but did not change the lipolysis sensitivity and the total amount of lipid in cells. Collectively, the results of this study provide evidence that PPM1D plays an important role in LD formation in mature adipocytes.
Type: article
URI: http://hdl.handle.net/2115/87085
Appears in Collections:理学院・理学研究院 (Graduate School of Science / Faculty of Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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