Decreased SIRT1 expression and LKB1 phosphorylation occur with long-term high-fat diet feeding, in addition to AMPK phosphorylation impairment in the early phase

Masayasu Yoneda; Ying Guo; Haruya Ono; Yusuke Nakatsu; Jun Zhang; Xinglong Cui; Misaki Iwashita; Sonoko Kumamoto; Yoshihiro Tsuchiya; Hideyuki Sakoda; Midori Fujishiro; Akifumi Kushiyama; Yuko Koketsu; Takako Kikuchi; Hideaki Kamata; Fusanori Nishimura; Tomoichiro Asano

doi:10.1016/j.orcp.2010.02.002

Decreased SIRT1 expression and LKB1 phosphorylation occur with long-term high-fat diet feeding, in addition to AMPK phosphorylation impairment in the early phase

Obes Res Clin Pract. 2010 Jul-Sep;4(3):e163-246. doi: 10.1016/j.orcp.2010.02.002.

Authors

Masayasu Yoneda¹, Ying Guo¹, Haruya Ono¹, Yusuke Nakatsu¹, Jun Zhang¹, Xinglong Cui¹, Misaki Iwashita¹, Sonoko Kumamoto¹, Yoshihiro Tsuchiya¹, Hideyuki Sakoda¹, Midori Fujishiro¹, Akifumi Kushiyama¹, Yuko Koketsu¹, Takako Kikuchi¹, Hideaki Kamata¹, Fusanori Nishimura¹, Tomoichiro Asano²

Affiliations

¹ 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.
² 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.

PMID: 24345663
DOI: 10.1016/j.orcp.2010.02.002

Abstract

Aims: 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.