Details

Autor(en) / Beteiligte

• Zhang, Min
• Wu, Pengbo
• Li, Ming
• Guo, Yitian
• Tian, Tian
• Liao, Xingchen
• Tan, Shiyun

Titel

Inhibition of Notch1 signaling reduces hepatocyte injury in nonalcoholic fatty liver disease via autophagy

Ist Teil von

• Biochemical and biophysical research communications, 2021-04, Vol.547, p.131-138

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease worldwide and an urgent target for clinical intervention. Notch1 signaling pathway activity was found to be related to the severity of NAFLD, but the specific mechanism is not precise. Here, we investigated the potential mechanisms of Notch1 signaling in the development of NAFLD. Firstly, we found that Notch1 signaling is activated in free fatty acids-treated HepG2 cells accompanied by lipid accumulation, apoptosis, oxidative stress, and mitochondrial damage, which could be alleviated by Notch1 inhibitor N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT). In the meantime, we found that administration of DAPT activated the autophagy pathway in NAFLD. Furthermore, the use of autophagy inhibitor chloroquine reversed the DAPT-mediated protective effect in NAFLD. All our results uncover a vital role of Notch1 in hepatocyte injury and metabolism of NAFLD, giving rise to a new sight for NAFLD treatment by regulation of Notch signaling and autophagy pathway. •Notch1 signaling pathway is elevated in NAFLD.•Inhibition of Notch1 alleviates lipid accumulation, oxidative stress, hepatocyte apoptosis and damage in NAFLD.•Inhibition of Notch1 protects NAFLD by promoting impaired autophagy.•Targeted inhibition of Notch1 may be a new idea for the treatment of NAFLD.