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.

Wan-jun Zhao;Yang-ping Bian;Qiu-hui Wang;Fei Yin;Li Yin;Yong-Ian Zhang;Jian-hui Liu

Chongqing Key Lab of Medicinal Chemistry&Molecular Pharmacology,Chongqing University of Technology,Chongqing 400054,China;College of Pharmacy and Bioengineering,Chongqing University of Technology,Chongqing 400054,China

中国药理学报（英文版）

[1]Wan-jun Zhao;Yang-ping Bian;Qiu-hui Wang;Fei Yin;Li Yin;Yong-Ian Zhang;Jian-hui Liu-.Blueberry-derived exosomes-like nanoparticles ameliorate nonalcoholic fatty liver disease by attenuating mitochondrial oxidative stress)[J].中国药理学报（英文版）,2022(03):645-658

BELNs,Preincubation,preincubation

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