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Pemafibrate Protects against Fatty Acid-Induced Nephropathy by Maintaining Renal Fatty Acid Metabolism

As classical agonists for peroxisomal proliferator-activated receptor alpha (PPARα), fibrates activate renal fatty acid metabolism (FAM) and provide renoprotection. However, fibrate prescription is limited in patients with kidney disease, since impaired urinary excretion of the drug causes serious a...

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Autores principales: Aomura, Daiki, Harada, Makoto, Yamada, Yosuke, Nakajima, Takero, Hashimoto, Koji, Tanaka, Naoki, Kamijo, Yuji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230306/
https://www.ncbi.nlm.nih.gov/pubmed/34207854
http://dx.doi.org/10.3390/metabo11060372
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author Aomura, Daiki
Harada, Makoto
Yamada, Yosuke
Nakajima, Takero
Hashimoto, Koji
Tanaka, Naoki
Kamijo, Yuji
author_facet Aomura, Daiki
Harada, Makoto
Yamada, Yosuke
Nakajima, Takero
Hashimoto, Koji
Tanaka, Naoki
Kamijo, Yuji
author_sort Aomura, Daiki
collection PubMed
description As classical agonists for peroxisomal proliferator-activated receptor alpha (PPARα), fibrates activate renal fatty acid metabolism (FAM) and provide renoprotection. However, fibrate prescription is limited in patients with kidney disease, since impaired urinary excretion of the drug causes serious adverse effects. Pemafibrate (PEM), a novel selective PPARα modulator, is mainly excreted in bile, and, thus, may be safe and effective in kidney disease patients. It remains unclear, however, whether PEM actually exhibits renoprotective properties. We investigated this issue using mice with fatty acid overload nephropathy (FAON). PEM (0.5 mg/kg body weight/day) or a vehicle was administered for 20 days to 13-week-old wild-type male mice, which were simultaneously injected with free fatty acid (FFA)-binding bovine serum albumin from day 7 to day 20 to induce FAON. All mice were sacrificed on day 20 for assessment of the renoprotective effect of PEM against FAON. PEM significantly attenuated the histological findings of tubular injury caused by FAON, increased the renal expressions of mRNA and proteins related to FAM, and decreased renal FFA content and oxidative stress. Taken together, PEM exhibits renoprotective effects through the activation and maintenance of renal FAM and represents a promising drug for kidney disease.
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spelling pubmed-82303062021-06-26 Pemafibrate Protects against Fatty Acid-Induced Nephropathy by Maintaining Renal Fatty Acid Metabolism Aomura, Daiki Harada, Makoto Yamada, Yosuke Nakajima, Takero Hashimoto, Koji Tanaka, Naoki Kamijo, Yuji Metabolites Article As classical agonists for peroxisomal proliferator-activated receptor alpha (PPARα), fibrates activate renal fatty acid metabolism (FAM) and provide renoprotection. However, fibrate prescription is limited in patients with kidney disease, since impaired urinary excretion of the drug causes serious adverse effects. Pemafibrate (PEM), a novel selective PPARα modulator, is mainly excreted in bile, and, thus, may be safe and effective in kidney disease patients. It remains unclear, however, whether PEM actually exhibits renoprotective properties. We investigated this issue using mice with fatty acid overload nephropathy (FAON). PEM (0.5 mg/kg body weight/day) or a vehicle was administered for 20 days to 13-week-old wild-type male mice, which were simultaneously injected with free fatty acid (FFA)-binding bovine serum albumin from day 7 to day 20 to induce FAON. All mice were sacrificed on day 20 for assessment of the renoprotective effect of PEM against FAON. PEM significantly attenuated the histological findings of tubular injury caused by FAON, increased the renal expressions of mRNA and proteins related to FAM, and decreased renal FFA content and oxidative stress. Taken together, PEM exhibits renoprotective effects through the activation and maintenance of renal FAM and represents a promising drug for kidney disease. MDPI 2021-06-09 /pmc/articles/PMC8230306/ /pubmed/34207854 http://dx.doi.org/10.3390/metabo11060372 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Aomura, Daiki
Harada, Makoto
Yamada, Yosuke
Nakajima, Takero
Hashimoto, Koji
Tanaka, Naoki
Kamijo, Yuji
Pemafibrate Protects against Fatty Acid-Induced Nephropathy by Maintaining Renal Fatty Acid Metabolism
title Pemafibrate Protects against Fatty Acid-Induced Nephropathy by Maintaining Renal Fatty Acid Metabolism
title_full Pemafibrate Protects against Fatty Acid-Induced Nephropathy by Maintaining Renal Fatty Acid Metabolism
title_fullStr Pemafibrate Protects against Fatty Acid-Induced Nephropathy by Maintaining Renal Fatty Acid Metabolism
title_full_unstemmed Pemafibrate Protects against Fatty Acid-Induced Nephropathy by Maintaining Renal Fatty Acid Metabolism
title_short Pemafibrate Protects against Fatty Acid-Induced Nephropathy by Maintaining Renal Fatty Acid Metabolism
title_sort pemafibrate protects against fatty acid-induced nephropathy by maintaining renal fatty acid metabolism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230306/
https://www.ncbi.nlm.nih.gov/pubmed/34207854
http://dx.doi.org/10.3390/metabo11060372
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