Betulinic acid improves nonalcoholic fatty liver disease through YY1/FAS signaling pathway.
Animals
Fatty Acid Synthase, Type I
/ metabolism
Fatty Acids
/ metabolism
Hep G2 Cells
Hepatocytes
/ drug effects
Humans
Liver
/ drug effects
Male
Mice
Mice, Inbred C57BL
Non-alcoholic Fatty Liver Disease
/ drug therapy
Pentacyclic Triterpenes
/ therapeutic use
Protective Agents
/ therapeutic use
YY1 Transcription Factor
/ metabolism
Betulinic Acid
NAFLD
Yin Yang 1
betulinic acid
fatty acid synthase
triglyceride
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
10
03
2020
revised:
14
07
2020
accepted:
27
07
2020
pubmed:
11
8
2020
medline:
12
3
2021
entrez:
11
8
2020
Statut:
ppublish
Résumé
The increasing prevalence of nonalcoholic fatty liver disease (NAFLD) worldwide indicates the urgent need to develop novel and effective treatment strategies. Betulinic acid (BA), a naturally occurring plant-derived pentacyclic triterpenoid, has an outstanding effect in improving metabolism. However, the pharmacological action and mechanism of BA in NAFLD remain unclear. Here, we show that BA-treated high-fat diet mice and methionine-choline deficient diet-fed mice are resistant to hepatic steatosis when compared with vehicle-treated mice. BA alleviates fatty acid synthesis, fibrosis, and inflammation and promotes fatty acid oxidation. Meanwhile, fatty acid synthase (FAS) expression and activity are markedly inhibited with BA treatment both in vitro and in vivo. Moreover, BA inhibits FAS expression through transcriptional suppression of Yin Yang 1 (YY1), leading to retard hepatocytes triglyceride accumulation. Collectively, BA protects hepatocytes from abnormal lipid deposition in NAFLD through YY1/FAS pathway. Our findings establish a novel role of BA in representing a possible therapeutic strategy to reverse NAFLD.
Identifiants
pubmed: 32777136
doi: 10.1096/fj.202000546R
doi:
Substances chimiques
Fatty Acids
0
Pentacyclic Triterpenes
0
Protective Agents
0
YY1 Transcription Factor
0
Yy1 protein, mouse
0
Fasn protein, mouse
EC 2.3.1.85
Fatty Acid Synthase, Type I
EC 2.3.1.85
Betulinic Acid
4G6A18707N
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
13033-13048Informations de copyright
© 2020 Federation of American Societies for Experimental Biology.
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