REV-ERB agonism improves liver pathology in a mouse model of NASH.
Animals
Disease Models, Animal
Humans
Inflammation
/ metabolism
Lipogenesis
/ physiology
Liver
/ metabolism
Liver Cirrhosis
/ pathology
Mice
Non-alcoholic Fatty Liver Disease
/ drug therapy
Nuclear Receptor Subfamily 1, Group D, Member 1
/ drug effects
Obesity
/ metabolism
Pyrrolidines
/ pharmacology
Thiophenes
/ pharmacology
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
23
06
2020
accepted:
17
09
2020
entrez:
1
10
2020
pubmed:
2
10
2020
medline:
13
11
2020
Statut:
epublish
Résumé
Non-alcoholic fatty liver disease (NAFLD) affects a significant number of people worldwide and currently there are no pharmacological treatments. NAFLD often presents with obesity, insulin resistance, and in some cases cardiovascular diseases. There is a clear need for treatment options to alleviate this disease since it often progresses to much more the much more severe non-alcoholic steatohepatitis (NASH). The REV-ERB nuclear receptor is a transcriptional repressor that regulates physiological processes involved in the development of NAFLD including lipogenesis and inflammation. We hypothesized that pharmacologically activating REV-ERB would suppress the progression of fatty liver in a mouse model of NASH. Using REV-ERB agonist SR9009 in a mouse NASH model, we demonstrate the beneficial effects of REV-ERB activation that led to an overall improvement of hepatic health by suppressing hepatic fibrosis and inflammatory response.
Identifiants
pubmed: 33002003
doi: 10.1371/journal.pone.0236000
pii: PONE-D-20-19393
pmc: PMC7529425
doi:
Substances chimiques
Nuclear Receptor Subfamily 1, Group D, Member 1
0
Pyrrolidines
0
SR9009
0
Thiophenes
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0236000Subventions
Organisme : NIDDK NIH HHS
ID : F32 DK105845
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared no competing interests.
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