title: Decreased SIRT1 expression and LKB1 phosphorylation occur with long-term high-fat diet feeding, in addition to AMPK phosphorylation impairment in the early phase.
abstract: CONCLUSIONS
  
  
  
  OBJECTIVE
  Energy sensing systems including AMPK and SIRT1 play important roles in the regulation of hepatic gluconeogenesis and fatty acid oxidation. In this study, we investigated how hepatic LKB1-AMPK signaling and SIRT1 expression are altered after 2 or 8 weeks of HFD feeding.
  
  
  METHODS
  The livers of male mice fed a HFD or a standard diet for 2 or 8 weeks were removed. The expression and phosphorylation levels of LKB1, AMPK, ACC and TORC2, and SIRT1 expression levels were examined by immunoblotting.
  
  
  RESULTS
  In mice fed a HFD for 2 weeks, the phosphorylations of AMPKα and ACC were decreased without significant alterations in LKB1 phosphorylation or SIRT1 protein levels, while TORC2 protein levels were increased. In mice fed a HFD for 8 weeks, marked reductions in LKB1 phosphorylation and SIRT1 protein amount were observed in addition to the decreased phosphorylations of AMPKα and ACC.
  
  
  CONCLUSIONS
  The mechanisms underlying impaired energy sensing signaling differ with the duration of HFD feeding. In the early phase of HFD feeding, LKB1 and SIRT1 were not impaired, while in the later phase of HFD feeding, decreased SIRT1 expression and LKB1 phosphorylation may be involved in the development of severe glucose and lipid intolerance.
authors.affiliation: Department of Medical Chemistry, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Masayasu
authors.initials: M
authors.lastname: Yoneda
authors.affiliation: Department of Medical Chemistry, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Ying
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Medical Chemistry, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Haruya
authors.initials: H
authors.lastname: Ono
authors.affiliation: Department of Medical Chemistry, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakatsu
authors.affiliation: Department of Medical Chemistry, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Medical Chemistry, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Xinglong
authors.initials: X
authors.lastname: Cui
authors.affiliation: Department of Medical Chemistry, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Misaki
authors.initials: M
authors.lastname: Iwashita
authors.affiliation: Department of Medical Chemistry, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Sonoko
authors.initials: S
authors.lastname: Kumamoto
authors.affiliation: Department of Medical Chemistry, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Tsuchiya
authors.affiliation: Department of Medical Chemistry, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Sakoda
authors.affiliation: Department of Medical Chemistry, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Fujishiro
authors.affiliation: Department of Medical Chemistry, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Kushiyama
authors.affiliation: Department of Medical Chemistry, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Koketsu
authors.affiliation: Department of Medical Chemistry, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Takako
authors.initials: T
authors.lastname: Kikuchi
authors.affiliation: Department of Medical Chemistry, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kamata
authors.affiliation: Department of Medical Chemistry, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Fusanori
authors.initials: F
authors.lastname: Nishimura
authors.affiliation: Department of Medical Chemistry, Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. Electronic address:tasano@hiroshima-u.ac.jp.
authors.forename: Tomoichiro
authors.initials: T
authors.lastname: Asano