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Title: Bempedoic Acid Restores Liver H2S Production in a Female Sprague-Dawley Rat Dietary Model of Non-Alcoholic Fatty Liver
Author: Roglans i Ribas, Núria
Fauste, Elena
Bentanachs Raset, Roger
Velázquez, Ana Magdalena
Pérez-Armas, Madelin
Donis, Cristina
Panadero, María I
Alegret i Jordà, Marta
Otero, Paola
Bocos, Carlos
Laguna Egea, Juan Carlos
Keywords: Fetge
Malalties del fetge
Liver diseases
Issue Date: 28-Dec-2022
Publisher: MDPI
Abstract: We previously demonstrated that treatment with BemA (bempedoic acid), an inhibitor of ATP citrate lyase, significantly reduces fatty liver in a model of liver steatosis (HFHFr-female Sprague-Dawley rat fed a high-fat high-fructose diet). Since the hepatic production of the gasotransmitter H2S is impaired in liver disorders, we were interested in determining if the production of H2S was altered in our HFHFr model and whether the administration of BemA reversed these changes. We used stored liver samples from a previous study to determine the total and enzymatic H2S production, as well as the expression of CBS (cystathionine β-synthase), CSE (cystathionine γ-lyase), and 3MST (3-mercaptopiruvate sulfurtransferase), and the expression/activity of FXR (farnesoid X receptor), a transcription factor involved in regulating CSE expression. Our data show that the HFHFr diet reduces the total and enzymatic production of liver H2S, mainly by decreasing the expression of CBS and CSE. Furthermore, BemA treatment restored H2S production, increasing the expression of CBS and CSE, providing evidence for the involvement of FXR transcriptional activity and the mTORC1 (mammalian target of rapamycin1)/S6K1 (ribosomal protein S6 kinase beta-1)/PGC1α (peroxisome proliferator receptor gamma coactivator1α) pathway. Keywords: FXR; NAFLD; PGC1α; S6K1; fructose; high-fat diet; mTORC1.
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It is part of: International Journal of Molecular Sciences, 2022, vol. 24, num. 1, p. 473
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ISSN: 1661-6596
Appears in Collections:Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)

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