title: Major role of apolipoprotein B in cycloheximide-induced acute hepatic steatosis in mice.
abstract: OBJECTIVE
  Hepatic steatosis accompanied by impaired protein synthesis is often observed in hepatic dysfunction. To assess whether protein synthesis inhibition directly induces hepatic steatosis, we investigated the molecular mechanisms of cycloheximide (CHX)-induced fatty liver mice.
  
  
  METHODS
  C57/BL6CR mice were i.p. administrated CHX (20 mg/kg) three times every 4 h to induce hepatic steatosis. Hepatic lipid secretion, fatty acid oxidation, hepatic lipogenesis and hepatic lipid uptake were evaluated.
  
  
  RESULTS
  Twenty-four hours after the first CHX injection, hepatic lipid levels increased in CHX-treated mice to 1.8-fold of that in controls but returned to normal within 48 h. The hepatic triglyceride (TG) secretion rate decreased significantly to 22% of controls, and the apolipoprotein B (apoB) protein level, but not microsomal TG transfer protein, decreased in CHX-treated mice. The apob gene expression was not significantly different between controls and CHX-treated mice. On the other hand, plasma free fatty acid and lipogenic protein levels did not increase and plasma β-hydroxybutyrate level remained stable, suggesting that the coordinated balance between fatty acid oxidation, hepatic lipid uptake and lipogenesis was not disrupted in this model. Cellular lipid accumulation and decreased cellular and secreted apoB were also observed in CHX-treated HepG2 cells. Knockdown of apoB in HepG2 cells also resulted in the cellular TG accumulation.
  
  
  CONCLUSIONS
  We demonstrated that decreased hepatic lipid secretion due to acute apoB reduction is involved in the pathogenesis of CHX-induced liver steatosis.
authors.affiliation: Department of Pediatrics, Osaka University Graduate School of Medicine, Suita Department of Pediatrics, Setsunan General Hospital, Kadoma, Osaka, Japan Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
authors.forename: Mari
authors.initials: M
authors.lastname: Murakami
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Bessho
authors.forename: Sotaro
authors.initials: S
authors.lastname: Mushiake
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kondou
authors.forename: Yoko
authors.initials: Y
authors.lastname: Miyoshi
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ozono