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Gene Expression Profiles Induced by a Novel Selective Peroxisome Proliferator-Activated Receptor α Modulator (SPPARMα) Pemafibrate

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 activ...

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Autores principales: Sasaki, Yusuke, Raza-Iqbal, Sana, Tanaka, Toshiya, Murakami, Kentaro, Anai, Motonobu, Osawa, Tsuyoshi, Matsumura, Yoshihiro, Sakai, Juro, Kodama, Tatsuhiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888257/
https://www.ncbi.nlm.nih.gov/pubmed/31766193
http://dx.doi.org/10.3390/ijms20225682
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author Sasaki, Yusuke
Raza-Iqbal, Sana
Tanaka, Toshiya
Murakami, Kentaro
Anai, Motonobu
Osawa, Tsuyoshi
Matsumura, Yoshihiro
Sakai, Juro
Kodama, Tatsuhiko
author_facet Sasaki, Yusuke
Raza-Iqbal, Sana
Tanaka, Toshiya
Murakami, Kentaro
Anai, Motonobu
Osawa, Tsuyoshi
Matsumura, Yoshihiro
Sakai, Juro
Kodama, Tatsuhiko
author_sort Sasaki, Yusuke
collection PubMed
description 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.
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spelling pubmed-68882572019-12-09 Gene Expression Profiles Induced by a Novel Selective Peroxisome Proliferator-Activated Receptor α Modulator (SPPARMα) Pemafibrate Sasaki, Yusuke Raza-Iqbal, Sana Tanaka, Toshiya Murakami, Kentaro Anai, Motonobu Osawa, Tsuyoshi Matsumura, Yoshihiro Sakai, Juro Kodama, Tatsuhiko Int J Mol Sci Review 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. MDPI 2019-11-13 /pmc/articles/PMC6888257/ /pubmed/31766193 http://dx.doi.org/10.3390/ijms20225682 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Sasaki, Yusuke
Raza-Iqbal, Sana
Tanaka, Toshiya
Murakami, Kentaro
Anai, Motonobu
Osawa, Tsuyoshi
Matsumura, Yoshihiro
Sakai, Juro
Kodama, Tatsuhiko
Gene Expression Profiles Induced by a Novel Selective Peroxisome Proliferator-Activated Receptor α Modulator (SPPARMα) Pemafibrate
title Gene Expression Profiles Induced by a Novel Selective Peroxisome Proliferator-Activated Receptor α Modulator (SPPARMα) Pemafibrate
title_full Gene Expression Profiles Induced by a Novel Selective Peroxisome Proliferator-Activated Receptor α Modulator (SPPARMα) Pemafibrate
title_fullStr Gene Expression Profiles Induced by a Novel Selective Peroxisome Proliferator-Activated Receptor α Modulator (SPPARMα) Pemafibrate
title_full_unstemmed Gene Expression Profiles Induced by a Novel Selective Peroxisome Proliferator-Activated Receptor α Modulator (SPPARMα) Pemafibrate
title_short Gene Expression Profiles Induced by a Novel Selective Peroxisome Proliferator-Activated Receptor α Modulator (SPPARMα) Pemafibrate
title_sort gene expression profiles induced by a novel selective peroxisome proliferator-activated receptor α modulator (spparmα) pemafibrate
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888257/
https://www.ncbi.nlm.nih.gov/pubmed/31766193
http://dx.doi.org/10.3390/ijms20225682
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