BI-3231, an enzymatic inhibitor of HSD17B13, reduces lipotoxic effects induced by palmitic acid in murine and human hepatocytes-Reference-Cited by-同舟云学术

BI-3231, an enzymatic inhibitor of HSD17B13, reduces lipotoxic effects induced by palmitic acid in murine and human hepatocytes

Published:2024-03-01 Issue:3 Volume:326 Page:C880-C892
ISSN:0363-6143
Container-title:American Journal of Physiology-Cell Physiology
language:en
Short-container-title:American Journal of Physiology-Cell Physiology

Author:

Alcober-Boquet Lucia¹,Kraus Nico¹^ORCID,Huber Lisa Sophie²,Vutukuri Rajkumar²,Fuhrmann Dominik C.³,Stross Claudia¹,Schaefer Liliana²^ORCID,Scholich Klaus⁴,Zeuzem Stefan¹,Piiper Albrecht¹,Schulz Marcel H.⁵,Trebicka Jonel⁶^ORCID,Welsch Christoph¹^ORCID,Ortiz Cristina¹^ORCID

Affiliation:

1. Medical Clinic 1, Goethe University Frankfurt, University Hospital, Frankfurt, Germany

2. Faculty of Medicine, Institute of Pharmacology and Toxicology, Goethe University Frankfurt, Frankfurt, Germany

3. Faculty of Medicine, Institute of Biochemistry I, Goethe University Frankfurt, Frankfurt, Germany

4. Faculty of Medicine, Institute of Clinical Pharmacology, Goethe University Frankfurt, Frankfurt, Germany

5. Faculty of Medicine, Institute of Cardiovascular Regeneration, Goethe University Frankfurt, Frankfurt, Germany

6. Department of Internal Medicine B, University Hospital Münster, Münster, Germany

Abstract

17-β-Hydroxysteroid dehydrogenase 13 (HSD17B13) is a lipid droplet protein primarily expressed in the liver hepatocytes. HSD17B13 is associated with the clinical outcome of chronic liver diseases and is therefore a target for the development of drugs. Here, we demonstrate the promising therapeutic effect of BI-3231 as a potent inhibitor of HSD17B13 based on its ability to inhibit triglyceride accumulation in lipid droplets (LDs), restore lipid metabolism and homeostasis, and increase mitochondrial activity in vitro.

Funder

SFB 1177

SFB 1039

Landes-Offensive zur Entwicklung Wissenschaftlich-ökonomischer Exzellenz (LOEWE) of the State of Hessen

EnABLE Cluster

Publisher

American Physiological Society

Link

https://journals.physiology.org/doi/pdf/10.1152/ajpcell.00413.2023

Reference48 articles.

1. PREDICT identifies precipitating events associated with the clinical course of acutely decompensated cirrhosis

2. Trends and the course of liver cirrhosis and its complications in Germany: Nationwide population-based study (2005 to 2018)

3. Nonalcoholic Fatty Liver Disease as a Nexus of Metabolic and Hepatic Diseases

4. Mechanisms and disease consequences of nonalcoholic fatty liver disease

5. The global NAFLD epidemic