title: Ectopic expression of N-acetylglucosaminyltransferase V accelerates hepatic triglyceride synthesis.
abstract: OBJECTIVE
  Glycosylation changes induce various types of biological phenomena in human diseases. N-Acetylglucosaminyltransferase V (GnT-V) is one of the most important glycosyltransferases involved in cancer biology. Recently, many researchers have challenged studies of lipid metabolism in cancer. To elucidate the relationships between cancer and lipid metabolism more precisely, we investigated the effects of GnT-V on lipid metabolism. In this study, we investigated the effects of aberrant glycosylation by GnT-V on hepatic triglyceride production.
  
  
  METHODS
  We compared lipid metabolism in GnT-V transgenic (Tg) mice with that of wild-type (WT) mice fed with normal chow or a choline-deficient amino acid-defined (CDAA) diet in vivo. HepG2 cells and GnT-V transfectants of Hep3B cells were used in an in vitro study.
  
  
  RESULTS
  Serum triglyceride levels and hepatic very low-density lipoprotein (VLDL) secretion in Tg mice were significantly elevated compared with that of WT mice. Hepatic lipogenic genes (Lxrα, Srebp1, Fas and Acc) and VLDL secretion-related gene (Mttp1) were significantly higher in Tg mice. Expression of these genes was also significantly higher in GnT-V transfectants than in mock cells. Knockdown of GnT-V decreased, while both epidermal growth factor and transforming growth factor-β1 stimulation increased LXRα gene expression in HepG2 cells. Finally, we found that the blockade of VLDL secretion by CDAA diet induced massive hepatic steatosis in Tg mice.
  
  
  CONCLUSIONS
  Our study demonstrates that enhancement of hepatic GnT-V activity accelerates triglyceride synthesis and VLDL secretion. Glycosylation modification by GnT-V regulation could be a novel target for a therapeutic approach to lipid metabolism.
authors.affiliation: Departments of Molecular Biochemistry and Clinical Investigation, Suita, Japan.|Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, Suita, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kamada
authors.affiliation: Departments of Molecular Biochemistry and Clinical Investigation, Suita, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ebisutani
authors.affiliation: Departments of Molecular Biochemistry and Clinical Investigation, Suita, Japan.
authors.forename: Sachiho
authors.initials: S
authors.lastname: Kida
authors.affiliation: Departments of Molecular Biochemistry and Clinical Investigation, Suita, Japan.
authors.forename: Kayo
authors.initials: K
authors.lastname: Mizutani
authors.affiliation: Departments of Molecular Biochemistry and Clinical Investigation, Suita, Japan.
authors.forename: Maaya
authors.initials: M
authors.lastname: Akita
authors.affiliation: Departments of Molecular Biochemistry and Clinical Investigation, Suita, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Yamamoto
authors.affiliation: Departments of Molecular Biochemistry and Clinical Investigation, Suita, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Fujii
authors.affiliation: Departments of Molecular Biochemistry and Clinical Investigation, Suita, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Sobajima
authors.affiliation: Departments of Molecular Biochemistry and Clinical Investigation, Suita, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Terao
authors.affiliation: Departments of Molecular Biochemistry and Clinical Investigation, Suita, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Takamatsu
authors.affiliation: Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, Suita, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Gastroenterology and Hepatology, Osaka University, Graduate School of Medicine, Suita, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Takehara
authors.affiliation: Departments of Molecular Biochemistry and Clinical Investigation, Suita, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Miyoshi
keywords: cancer; glycosylation; lipid metabolism; liver X receptor alpha; very low-density lipoprotein