Pemafibrate, a selective PPARα modulator, and fenofibrate suppress microglial activation through distinct PPARα and SIRT1-dependent pathways
Copyright © 2020 Elsevier Inc. All rights reserved..
Pemafibrate, a selective peroxisome proliferator-activated receptor (PPAR) α modulator, is a new drug that specifically modulates PPARα conformation and co-activator recruitment, thereby lowers plasma triglycerides with less off-target effects. Classical PPARα ligands such as fenofibrate suppress inflammatory cells including microglia. However, effects of pemafibrate on microglia have never been addressed. Here we show that pemafibrate, like other PPARα ligands, potently suppressed NF-κB phosphorylation and cytokine expression in microglial cells. PPARα knockdown significantly amplified LPS-induced cytokine expression. Pemafibrate-induced suppression of IL-6 expression was reversed by PPARα knockdown. However, suppression by fenofibrate was not reversed by PPARα knockdown but by Sirtuin 1 (SIRT1) knockdown. In conclusion, pemafibrate and fenofibrate similarly suppresses microglial activation but through distinct PPARα and SIRT1-dependet pathways.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:524 |
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| Enthalten in: |
Biochemical and biophysical research communications - 524(2020), 2 vom: 02. Apr., Seite 385-391 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ogawa, Kento [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 16.10.2020 Date Revised 16.10.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbrc.2020.01.118 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM306011751 |
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| 100 | 1 | |a Ogawa, Kento |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Pemafibrate, a selective PPARα modulator, and fenofibrate suppress microglial activation through distinct PPARα and SIRT1-dependent pathways |
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| 500 | |a published: Print-Electronic | ||
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| 520 | |a Copyright © 2020 Elsevier Inc. All rights reserved. | ||
| 520 | |a Pemafibrate, a selective peroxisome proliferator-activated receptor (PPAR) α modulator, is a new drug that specifically modulates PPARα conformation and co-activator recruitment, thereby lowers plasma triglycerides with less off-target effects. Classical PPARα ligands such as fenofibrate suppress inflammatory cells including microglia. However, effects of pemafibrate on microglia have never been addressed. Here we show that pemafibrate, like other PPARα ligands, potently suppressed NF-κB phosphorylation and cytokine expression in microglial cells. PPARα knockdown significantly amplified LPS-induced cytokine expression. Pemafibrate-induced suppression of IL-6 expression was reversed by PPARα knockdown. However, suppression by fenofibrate was not reversed by PPARα knockdown but by Sirtuin 1 (SIRT1) knockdown. In conclusion, pemafibrate and fenofibrate similarly suppresses microglial activation but through distinct PPARα and SIRT1-dependet pathways | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Dyslipidemia | |
| 650 | 4 | |a Fibrate | |
| 650 | 4 | |a Inflammation | |
| 650 | 4 | |a Microglia | |
| 650 | 4 | |a Peroxisome proliferator-activated receptor | |
| 650 | 4 | |a Sirtuin 1 | |
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| 650 | 7 | |a Anti-Inflammatory Agents |2 NLM | |
| 650 | 7 | |a Benzoxazoles |2 NLM | |
| 650 | 7 | |a Butyrates |2 NLM | |
| 650 | 7 | |a PPAR alpha |2 NLM | |
| 650 | 7 | |a Sirtuin 1 |2 NLM | |
| 650 | 7 | |a EC 3.5.1.- |2 NLM | |
| 700 | 1 | |a Yagi, Takashi |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Tingting |e verfasserin |4 aut | |
| 700 | 1 | |a Takeda, Katsushi |e verfasserin |4 aut | |
| 700 | 1 | |a Ohguchi, Hideomi |e verfasserin |4 aut | |
| 700 | 1 | |a Koyama, Hiroyuki |e verfasserin |4 aut | |
| 700 | 1 | |a Aotani, Daisuke |e verfasserin |4 aut | |
| 700 | 1 | |a Imaeda, Kenro |e verfasserin |4 aut | |
| 700 | 1 | |a Kataoka, Hiromi |e verfasserin |4 aut | |
| 700 | 1 | |a Tanaka, Tomohiro |e verfasserin |4 aut | |
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