2. Academic Validation
  3. Pemafibrate, a selective PPARα modulator, and fenofibrate suppress microglial activation through distinct PPARα and SIRT1-dependent pathways

Pemafibrate, a selective PPARα modulator, and fenofibrate suppress microglial activation through distinct PPARα and SIRT1-dependent pathways

  • Biochem Biophys Res Commun. 2020 Apr 2;524(2):385-391. doi: 10.1016/j.bbrc.2020.01.118.
Kento Ogawa 1,  Takashi Yagi 1,  Tingting Guo 1,  Katsushi Takeda 1,  Hideomi Ohguchi 1,  Hiroyuki Koyama 1,  Daisuke Aotani 1,  Kenro Imaeda 2,  Hiromi Kataoka 1,  Tomohiro Tanaka 3
Affiliations

Affiliations

  • 1 Department of Gastroenterology and Metabolism, Nagoya City University, Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan.
  • 2 Department of Endocrinology and Diabetes, Nagoya City West Medical Center, 1-1-1 Hirate-cho, Kita-ku, Nagoya, 462-8508, Japan.
  • 3 Department of Gastroenterology and Metabolism, Nagoya City University, Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan. Electronic address: tttanaka@med.negoya-cu.ac.jp.
PMID: 32005522 DOI: 10.1016/j.bbrc.2020.01.118
Abstract

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.

Keywords

Dyslipidemia; Fibrate; Inflammation; Microglia; Peroxisome proliferator-activated receptor; Sirtuin 1.

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