Gene expression profiles induced by a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMΑ) pemafibrate

Yusuke Sasaki, Sana Raza-Iqbal, Toshiya Tanaka, Kentaro Murakami, Motonobu Anai, Tsuyoshi Osawa, Yoshihiro Matsumura, Juro Sakai, Tatsuhiko Kodama

Research output: Contribution to journalReview articlepeer-review

5 Citations (Scopus)

Abstract

Pemafibrate is the first clinically-available selective peroxisome proliferator-activated receptor α modulator (SPPARMα) that has been shown to effectively improve hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) levels. Global gene expression analysis reveals that the activation of PPARα by pemafibrate induces fatty acid (FA) uptake, binding, and mitochondrial or peroxisomal oxidation as well as ketogenesis in mouse liver. Pemafibrate most profoundly induces HMGCS2 and PDK4, which regulate the rate-limiting step of ketogenesis and glucose oxidation, respectively, compared to other fatty acid metabolic genes in human hepatocytes. This suggests that PPARα plays a crucial role in nutrient flux in the human liver. Additionally, pemafibrate induces clinically favorable genes, such as ABCA1, FGF21, and VLDLR. Furthermore, pemafibrate shows anti-inflammatory effects in vascular endothelial cells. Pemafibrate is predicted to exhibit beneficial effects in patients with atherogenic dyslipidemia and diabetic microvascular complications.

Original languageEnglish
Article number5682
JournalInternational journal of molecular sciences
Volume20
Issue number22
DOIs
Publication statusPublished - 2019 Nov

Keywords

  • ASCVD
  • EndMT
  • Fatty acid β-oxidation
  • Ketogenesis
  • Pemafibrate
  • SPPARMα

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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