The Hebrew University of Jerusalem, Faculty of Agricultural, Food and Environmental Quality Sciences, Institute of Biochemistry, Food Science and Nutrition, Rehovot, Israel.
Obesity (Silver Spring). 2010 Jun;18(6):1108-15. doi: 10.1038/oby.2009.489. Epub 2010 Jan 7.
The primary objective of this study was to investigate the impact of lipid oversupply on the AMPK pathway in skeletal muscle, liver, and adipose tissue. Male Wistar rats were infused with lipid emulsion (LE) or phosphate-buffered saline for 5 h/day for 6 days. Muscles exposed to LE for 6 days exhibited increased AMPK and acetyl-CoA carboxylase (ACC) phosphorylation, along with a greater association between AMPK and Ca(2+)/calmodulin-dependent protein kinase kinase (CaMKK). No differences in muscle protein phosphatase 2C (PP2C) activity, LKB1 phosphorylation or AMPK and LKB1 association were observed. Muscle ACCbeta, and adiponectin receptor 1 (AdipoR1) mRNA levels and PPARgamma-co-activator 1alpha (PGC1alpha) protein levels were also increased in LE-treated rats. In contrast, AMPK and ACC phosphorylation decreased and PP2C activity increased in rat livers exposed to LE. Hepatic mRNA levels of ACCalpha, PPARalpha, AdipoR1, AdipoR2, and sterol regulatory element-binding protein-1c (SREBP1c) were also reduced after LE infusion. In adipose tissue, there was no significant alteration in AMPK or ACC phosphorylation. These results demonstrate that following lipid oversupply the AMPK pathway was enhanced in rat skeletal muscle while diminished in the liver and was unchanged in adipose tissue. CaMKK in skeletal muscle and PP2C in the liver, at least in part, appear to mediate these alterations. Alterations in AMPK pathway in the liver induced metabolic defects associated with lipid oversupply.
本研究的主要目的是探讨脂质过负荷对骨骼肌、肝脏和脂肪组织中 AMPK 通路的影响。雄性 Wistar 大鼠每天输注脂肪乳剂（LE）或磷酸盐缓冲盐水 5 小时，持续 6 天。暴露于 LE 6 天的肌肉表现出 AMPK 和乙酰辅酶 A 羧化酶（ACC）磷酸化增加，以及 AMPK 与钙/钙调蛋白依赖性蛋白激酶激酶（CaMKK）之间的关联增强。肌肉蛋白磷酸酶 2C（PP2C）活性、LKB1 磷酸化或 AMPK 和 LKB1 关联没有差异。LE 处理的大鼠肌肉 ACCβ和脂联素受体 1（AdipoR1）mRNA 水平和过氧化物酶体增殖物激活受体γ共激活因子 1α（PGC1α）蛋白水平也增加。相反，暴露于 LE 的大鼠肝脏中 AMPK 和 ACC 磷酸化减少，PP2C 活性增加。LE 输注后，肝脏中 ACCα、PPARα、AdipoR1、AdipoR2 和固醇调节元件结合蛋白-1c（SREBP1c）的 mRNA 水平也降低。脂肪组织中 AMPK 或 ACC 磷酸化没有明显变化。这些结果表明，脂质过负荷后，AMPK 通路在大鼠骨骼肌中增强，而在肝脏中减弱，在脂肪组织中不变。至少部分原因是肌肉中的 CaMKK 和肝脏中的 PP2C 介导了这些变化。肝脏中 AMPK 通路的改变诱导与脂质过负荷相关的代谢缺陷。
