Blueberry-derived exosomes-like nanoparticles ameliorate nonalcoholic fatty liver disease by attenuating mitochondrial oxidative stress

• 作者: Wan-jun Zhao Yang-ping Bian Qiu-hui Wang Fei Yin Li Yin Yong-Ian Zhang Jian-hui Liu
• 来源期刊: 中国药理学报（英文版）
• 年，卷（期）: 2022,（3）
• 所属期刊栏目: Molecular,Hepatic,and Renal Pharmacology
• 页码范围: 645-658
• 页数: 14页
• 语种: 英文

摘要

Accumulating evidence indicates that mitochondrial dysfunction and oxidative stress play a pivotal role in the initiation and progression of nonalcoholic fatty liver disease(NAFLD).In this study,we found that blueberry-derived exosomes-like nanoparticles(BELNs)could ameliorate oxidative stress in rotenone-induced HepG2 cells and high-fat diet(HFD)-fed C57BL/6 mice.Preincubation with BELNs decreased the level of reactive oxygen species(ROS),increased the mitochondrial membrane potential,and prevented cell apoptosis by inducing the expression of Bcl-2 and heme oxygenase-1(HO-1)and decreasing the content of Bax in rotenone-treated HepG2 cells.We also found that preincubation with BELNs accelerated the translocation of Nrf2,an important transcription factor of antioxidative proteins,from the cytoplasm to the nucleus in rotenone-treated HepG2 cells.Moreover,administration of BELNs improved insulin resistance,ameliorated the dysfunction of hepatocytes,and regulated the expression of detoxifying/antioxidant genes by affecting the distribution of Nrf2 in the cytoplasm and nucleus of hepatocytes of HFD-fed mice.Furthermore,BELNs supplementation prevented the formation of vacuoles and attenuated the accumulation of lipid droplets by inhibiting the expression of fatty acid synthase(FAS)and acetyl-CoA carboxylase 1(ACC1),the two key transcription factors for de novo lipogenesis in the liver of HFD-fed mice.These findings suggested that BELNs can be used for the treatment of NAFLD because of their antioxidative activity.