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

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

来源：Obesity Research & Clinical Practice, 2010, 4(3): E201-E207.

DOI：10.1016/j.orcp.2010.02.002

• AMP-activated protein kinase (AMPK)
• Sirtuin 1 (SIRT1)
• High-fat diet (HFD)

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 AMPK alpha 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 AMPK alpha 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.

• 出版日期2010-9