Distinct Time Course of the Decrease in Hepatic AMP-Activated Protein Kinase and Akt Phosphorylation in Mice Fed a High Fat Diet

被引:15
|
作者
Shiwa, Mami [1 ]
Yoneda, Masayasu [1 ]
Okubo, Hirofumi [1 ]
Ohno, Haruya [1 ]
Kobuke, Kazuhiro [1 ]
Monzen, Yuko [1 ]
Kishimoto, Rui [1 ]
Nakatsu, Yusuke [2 ]
Asano, Tomoichiro [2 ]
Kohno, Nobuoki [1 ]
机构
[1] Hiroshima Univ, Dept Mol & Internal Med, Grad Sch Biomed & Hlth Sci, Hiroshima, Japan
[2] Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Dept Biomed Chem, Hiroshima, Japan
来源
PLOS ONE | 2015年 / 10卷 / 08期
关键词
MODERATE WEIGHT-REDUCTION; INSULIN-RESISTANCE; TISSUE INFLAMMATION; SKELETAL-MUSCLE; METABOLISM; REVERSAL; OBESITY; TERM; HYPERGLYCEMIA; SENSITIVITY;
D O I
10.1371/journal.pone.0135554
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
AMP-activated protein kinase (AMPK) plays an important role in insulin resistance, which is characterized by the impairment of the insulin-Akt signaling pathway. However, the time course of the decrease in AMPK and Akt phosphorylation in the liver during the development of obesity and insulin resistance caused by feeding a high fat diet (HFD) remains controversial. Moreover, it is unclear whether the impairment of AMPK and Akt signaling pathways is reversible when changing from a HFD to a standard diet (SD). Male ddY mice were fed the SD or HFD for 3 to 28 days, or fed the HFD for 14 days, followed by the SD for 14 days. We examined the time course of the expression and phosphorylation levels of AMPK and Akt in the liver by immunoblotting. After 3 days of feeding on the HFD, mice gained body weight, resulting in an increased oil red O staining, indicative of hepatic lipid accumulation, and significantly decreased AMPK phosphorylation, in comparison with mice fed the SD. After 14 days on the HFD, systemic insulin resistance occurred and Akt phosphorylation significantly decreased. Subsequently, a change from the HFD to SD for 3 days, after 14 days on the HFD, ameliorated the impairment of AMPK and Akt phosphorylation and systemic insulin resistance. Our findings indicate that AMPK phosphorylation decreases early upon feeding a HFD and emphasizes the importance of prompt lifestyle modification for decreasing the risk of developing diabetes.
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页数:12
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