Distinct Time Course of the Decrease in Hepatic AMP-Activated Protein Kinase and Akt Phosphorylation in Mice Fed a High Fat Diet.
Distinct Time Course of the Decrease in Hepatic AMP-Activated Protein Kinase and Akt Phosphorylation in Mice Fed a High Fat Diet.
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在喂养高脂肪饮食的小鼠中，肝AMP激活的蛋白激酶和Akt磷酸化的降低的明显时间过程。
DOI：
10.1371/journal.pone.0135554
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Kohno N
中科院分区：
文献类型：
--
作者：
Shiwa M;Yoneda M;Okubo H;Ohno H;Kobuke K;Monzen Y;Kishimoto R;Nakatsu Y;Asano T;Kohno N
腺苷酸活化蛋白激酶（AMPK）在胰岛素抵抗中起重要作用，其特征是胰岛素-Akt信号通路受损。然而，在由高脂饮食（HFD）引起的肥胖和胰岛素抵抗的发展过程中，肝脏中AMPK和Akt磷酸化降低的时间过程仍然存在争议。此外，尚不清楚从HFD变为标准饮食（SD）时AMPK和Akt信号通路的损伤是否可逆。雄性ddY小鼠饲喂SD或HFD 3至28天，或饲喂HFD 14天，然后饲喂SD 14天。我们通过免疫印迹检测了AMPK和Akt在肝脏中表达和磷酸化水平的时间过程。喂食HFD 3天后，与喂食SD的小鼠相比，小鼠体重增加，导致油红O染色增加，表明肝脏脂质蓄积，并且AMPK磷酸化显著降低。HFD治疗14天后，出现全身性胰岛素抵抗，Akt磷酸化水平显著降低。随后，从HFD到SD的变化持续3天，在HFD 14天后，改善了AMPK和Akt磷酸化和全身胰岛素抵抗的损害。我们的研究结果表明，AMPK磷酸化在喂食HFD后早期降低，并强调了及时改变生活方式对降低患糖尿病风险的重要性。
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.