Hepatic ERK activity plays a role in energy metabolism.
Hepatic ERK activity plays a role in energy metabolism.
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DOI：
10.1016/j.mce.2013.05.021
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发表时间：
2013-08-15
影响因子：
4.1
通讯作者：
Xu H
中科院分区：
文献类型：
--
作者：
Jiao P;Feng B;Li Y;He Q;Xu H
有丝分裂原活化蛋白激酶（MAPK），如c-Jun N-末端激酶（JNK）和P38，已被报道在能量稳态中起重要作用。在这项研究中，我们表明，细胞外信号调节激酶（ERK）的活性增加，在饮食诱导和遗传性肥胖小鼠的肝脏。通过过度表达组成性活性MAPK激酶1（MEK CA）激活瘦小鼠肝脏中的ERK，导致能量消耗减少，参与脂肪酸氧化的基因表达降低，增加空腹高血糖症并引起全身性胰岛素抵抗。有趣的是，与表达绿色荧光蛋白（GFP）的对照小鼠相比，在过表达MEK CA的小鼠中，肝糖原含量显著增加，G6 β基因表达降低，因此肝葡萄糖输出不太可能是高血糖症的主要贡献者。MEK CA降低G6 β基因表达的一个潜在机制可能是由于ERK介导的磷酸化和FOXO 1的胞浆滞留。从MEK CA小鼠中分离的脂肪细胞显示出脂肪分解增加。这些小鼠中游离脂肪酸（FFA）的循环水平也增加，这可能导致全身胰岛素抵抗和随后的高血糖症。与这些结果一致，敲低饮食诱导的肥胖（DIO）小鼠肝脏中的ERK表达改善全身胰岛素敏感性和葡萄糖耐量。这些结果表明，在DIO小鼠肝脏ERK活性增加可能有助于rincreased肝糖原含量和降低能量消耗的肥胖。
Mitogen activated protein kinases (MAPKs), such as c-Jun N-terminal kinase (JNK) and P38, have been reported to play important roles in energy homeostasis. In this study, we show that the activity of extracellular signal-regulated kinase (ERK) is increased in the livers of diet induced and genetically obese mice. Activation of ERK in the livers of lean mice by over-expressing the constitutively active MAPK kinase 1 (MEK CA) results in decreased energy expenditure, lowered expression of genes involved in fatty acid oxidation, increases fasting hyperglycemia and causes systemic insulin resistance. Interestingly, hepatic glycogen content is markedly increased and expression of G6Pase gene is decreased in mice over-expressing MEK CA compared to control mice expressing green fluorescent protein (GFP), therefore hepatic glucose output is not likely the major contributor of hyperglycemia. One potential mechanism of decreased expression of G6Pase gene by MEK CA is likely due to ERK mediated phosphorylation and cytosolic retention of FOXO1. Adipocytes isolated from MEK CA mice display increased lipolysis. Circulating levels of free fatty acids (FFAs) in these mice are also increased, which possibly contribute to systemic insulin resistance and subsequent hyperglycemia. Consistent with these results, knocking down ERK expression in the liver of diet induced obese (DIO) mice improves systemic insulin sensitivity and glucose tolerance. These results indicate that increased hepatic ERK activity in DIO mice may contribute to rincreased liver glycogen content and decreased energy expenditure in obesity.
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影响因子：
4.8
作者：
Asada, Sachie;Daitoku, Hiroaki;Fukamizu, Akiyoshi
通讯作者：
Fukamizu, Akiyoshi
影响因子：
4.8
作者：
Liu, Hui-Yu;Collins, Qu Fan;Cao, Wenhong
通讯作者：
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影响因子：
4.8
作者：
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通讯作者：
Farmer, SR
影响因子：
3.7
作者：
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通讯作者：
Xu H
影响因子：
8.2
作者：
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通讯作者：
Tanti, J. F.