title: Liver X receptor in cooperation with SREBP-1c is a major lipid synthesis regulator in nonalcoholic fatty liver disease.
abstract: OBJECTIVE
  Nonalcoholic fatty liver disease (NAFLD) is one of the most frequent causes of liver dysfunction and its incidence has increased markedly. However, the mechanisms involved in the pathogenesis of NAFLD in humans have not been thoroughly investigated. Sterol regulatory element binding protein (SREBP)-1c and carbohydrate responsive element binding protein (ChREBP) are transcriptional factors that regulate the expression of lipogenic genes, including acetyl-CoA carboxylases (ACCs) and fatty acid synthase (FAS). SREBP-1c and ChREBP are transactivated by liver X receptor (LXR), a nuclear receptor that regulates the metabolism of cholesterol and fatty acids. To understand the mechanisms involved in the pathogenesis of NAFLD, we investigated the transcriptional factors and lipogenic genes activated in the liver with NAFLD.
  
  
  METHODS
  Real-time PCR was carried out on liver biopsy samples from 20 NAFLD patients. The target genes studied were: ACC1, FAS, SREBP-1c, ChREBP, AMP-activated protein kinase (AMPK), and LXRalpha.
  
  
  RESULTS
  LXRalpha, SREBP-1c, ACC1, and FAS were upregulated in NAFLD patients. Expression levels of LXR were four times greater than those of the controls and correlated significantly with SREBP-1c, but not with ChREBP, levels.
  
  
  CONCLUSIONS
  These findings suggest that LXR acts as one of the main regulators of lipid metabolism by regulating SREBP-1c expression in NAFLD.
authors.affiliation: Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Japan.
authors.forename: Nobito
authors.initials: N
authors.lastname: Higuchi
authors.forename: Masaki
authors.initials: M
authors.lastname: Kato
authors.forename: Yuki
authors.initials: Y
authors.lastname: Shundo
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Tajiri
authors.forename: Masatake
authors.initials: M
authors.lastname: Tanaka
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamashita
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Kohjima
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kotoh
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakamuta
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Takayanagi
authors.forename: Munechika
authors.initials: M
authors.lastname: Enjoji