title: Down-regulation of SREBP-1c is associated with the development of burned-out NASH.
abstract: OBJECTIVE
  It is well-known that hepatic triglycerides (TG) diminish with the progression of non-alcoholic steatohepatitis (NASH), which has been designated as burned-out NASH, but its mechanism remains unclear. We aimed to explore the changes in hepatic fatty acid (FA) and TG metabolism with disease progression.
  
  
  METHODS
  Hepatic expression of key genes in healthy individuals (n=6) and patients with simple steatosis (SS, n=10), mild NASH (fibrosis stage 1-2, n=20), and advanced NASH (fibrosis stage 3-4, n=20) were assessed by quantitative polymerase chain reaction.
  
  
  RESULTS
  Hepatic expression of genes related to FA uptake and oxidation and very-low-density lipoprotein synthesis/export did not differ among the groups. However, the mRNA levels of sterol regulatory element-binding protein (SREBP)-1c and its downstream genes FA synthase, acetyl-coenzyme A carboxylase 1, and diacylglycerol acyltransferase 1 were inversely correlated with fibrosis stage. Immunoblot analysis revealed a remarkable reduction in mature SREBP-1c levels in advanced NASH. Furthermore, hepatic expression of tumor necrosis factor-alpha increased in accordance with fibrosis progression, which was possibly related to the decrease in hepatic SREBP-1c expression.
  
  
  CONCLUSIONS
  Down-regulation of SREBP-1c and lipogenic enzymes may be associated with the development of burned-out NASH.
authors.affiliation: Department of Gastroenterology, Shinshu University School of Medicine, Japan. naopi@shinshu-u.ac.jp
authors.forename: Tadanobu
authors.initials: T
authors.lastname: Nagaya
authors.forename: Naoki
authors.initials: N
authors.lastname: Tanaka
authors.forename: Takefumi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Kenji
authors.initials: K
authors.lastname: Sano
authors.forename: Akira
authors.initials: A
authors.lastname: Horiuchi
authors.forename: Michiharu
authors.initials: M
authors.lastname: Komatsu
authors.forename: Takero
authors.initials: T
authors.lastname: Nakajima
authors.forename: Tomoko
authors.initials: T
authors.lastname: Nishizawa
authors.forename: Satoru
authors.initials: S
authors.lastname: Joshita
authors.forename: Takeji
authors.initials: T
authors.lastname: Umemura
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ichijo
authors.forename: Akihiro
authors.initials: A
authors.lastname: Matsumoto
authors.forename: Kaname
authors.initials: K
authors.lastname: Yoshizawa
authors.forename: Jun
authors.initials: J
authors.lastname: Nakayama
authors.forename: Eiji
authors.initials: E
authors.lastname: Tanaka
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Aoyama
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D015536:Down-Regulation; D005234:Fatty Liver / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D012720:Severity of Illness Index; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides