Monoacylglycerol Lipase Inhibition Protects From Liver Injury in Mouse Models of Sclerosing Cholangitis.
ATP Binding Cassette Transporter, Subfamily B
/ genetics
Animals
Benzodioxoles
/ therapeutic use
Bile Acids and Salts
/ metabolism
Caco-2 Cells
Cholangitis, Sclerosing
/ complications
Cholestasis
/ complications
Disease Models, Animal
Enzyme Inhibitors
/ therapeutic use
Fatty Acids
/ metabolism
Humans
Liver Cirrhosis, Biliary
/ etiology
Male
Mice, Inbred C57BL
Mice, Knockout
Monoacylglycerol Lipases
/ antagonists & inhibitors
Piperidines
/ therapeutic use
Pyridines
/ toxicity
ATP-Binding Cassette Sub-Family B Member 4
Journal
Hepatology (Baltimore, Md.)
ISSN: 1527-3350
Titre abrégé: Hepatology
Pays: United States
ID NLM: 8302946
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
27
02
2019
accepted:
29
08
2019
pubmed:
11
9
2019
medline:
21
4
2021
entrez:
11
9
2019
Statut:
ppublish
Résumé
Monoacylglycerol lipase (MGL) is the last enzymatic step in triglyceride degradation, hydrolyzing monoglycerides into glycerol and fatty acids (FAs) and converting 2-arachidonoylglycerol into arachidonic acid, thus providing ligands for nuclear receptors as key regulators of hepatic bile acid (BA)/lipid metabolism and inflammation. We aimed to explore the role of MGL in the development of cholestatic liver and bile duct injury in mouse models of sclerosing cholangitis, a disease so far lacking effective pharmacological therapy. To this aim we analyzed the effects of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) feeding to induce sclerosing cholangitis in wild-type (WT) and knockout (MGL Collectively, our study unravels MGL as a metabolic target, demonstrating that MGL inhibition may be considered as potential therapy for sclerosing cholangitis.
Sections du résumé
BACKGROUND AND AIMS
Monoacylglycerol lipase (MGL) is the last enzymatic step in triglyceride degradation, hydrolyzing monoglycerides into glycerol and fatty acids (FAs) and converting 2-arachidonoylglycerol into arachidonic acid, thus providing ligands for nuclear receptors as key regulators of hepatic bile acid (BA)/lipid metabolism and inflammation. We aimed to explore the role of MGL in the development of cholestatic liver and bile duct injury in mouse models of sclerosing cholangitis, a disease so far lacking effective pharmacological therapy.
APPROACH AND RESULTS
To this aim we analyzed the effects of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) feeding to induce sclerosing cholangitis in wild-type (WT) and knockout (MGL
CONCLUSIONS
Collectively, our study unravels MGL as a metabolic target, demonstrating that MGL inhibition may be considered as potential therapy for sclerosing cholangitis.
Identifiants
pubmed: 31505038
doi: 10.1002/hep.30929
pmc: PMC7317927
doi:
Substances chimiques
3,5-diethoxycarbonyl-1,4-dihydrocollidine
0
ATP Binding Cassette Transporter, Subfamily B
0
Benzodioxoles
0
Bile Acids and Salts
0
Enzyme Inhibitors
0
Fatty Acids
0
JZL 184
0
Piperidines
0
Pyridines
0
Monoacylglycerol Lipases
EC 3.1.1.23
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1750-1765Subventions
Organisme : Austrian Science Fund FWF
ID : I2661
Pays : Austria
Informations de copyright
© 2019 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of American Association for the Study of Liver Diseases.
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