Mitochondrial biogenesis

Biology

Reactive oxygen species

Endocrinology

Lipogenesis

Rotenone

Biochemistry

Fatty liver

TFAM

Lipid droplet

Oxidative phosphorylation

Oxidative stress

Nonalcoholic fatty liver disease

Internal medicine

Mitochondrion

Lipid metabolism

Medicine

Chemistry

Disease

Acta Pharmacologica Sinica

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.

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