Betulinic acid improves nonalcoholic fatty liver disease through YY1/FAS signaling pathway.
FASEB J
; 34(9): 13033-13048, 2020 09.
Article
en En
| MEDLINE
| ID: mdl-32777136
ABSTRACT
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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Sustancias Protectoras
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Factor de Transcripción YY1
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Triterpenos Pentacíclicos
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Acido Graso Sintasa Tipo I
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Enfermedad del Hígado Graso no Alcohólico
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
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Humans
/
Male
Idioma:
En
Revista:
FASEB J
Asunto de la revista:
BIOLOGIA
/
FISIOLOGIA
Año:
2020
Tipo del documento:
Article