Hepatic triglyceride accumulation via endoplasmic reticulum stress-induced SREBP-1 activation is regulated by ceramide synthases

The endoplasmic reticulum (ER) is not only important for protein synthesis and folding but is also crucial for lipid synthesis and metabolism. In the current study, we demonstrate an important role of ceramide synthases (CerS) in ER stress and NAFLD progression. Ceramide is important in sphingolipid metabolism, and its acyl chain length is determined by a family of six CerS in mammals. CerS2 generates C22-C24 ceramides, and CerS5 or CerS6 produces C16 ceramide. To gain insight into the role of CerS in NAFLD, we used a high-fat diet (HFD)-induced NAFLD mouse model. Decreased levels of CerS2 and increased levels of CerS6 were observed in the steatotic livers of mice fed a HFD. In vitro experiments with Hep3B…

• NR
  National Research Foundation
• NR
  National Research Foundation of Korea

  Awards: NRF-2016R1D1A1B04930619, NRF-2016R1D1A1B03935706, NRF-2019R1F1A1057934
• IS
  Israel Science Foundation

  Award: 1728/15
• MO
  Ministry of Education, Science and Technology

  Award: NRF-2016R1D1A1B03935706