Abstract:
:Non-alcoholic fatty liver disease is the most commonly occurring chronic liver disease, and hepatic steatosis, a condition defined as extensive lipid accumulation in hepatocytes, is associated with liver dysfunction and metabolic diseases, such as, obesity and type II diabetes. Apelin is an adipokine that acts on a G protein-coupled receptor named APJ, and has been established to play pivotal roles in various physiological conditions. However, the function of apelin in hepatocytes has not been fully investigated. In order to assess the functional roles of apelin and APJ in hepatocytes, we used an in vitro model of liver X receptor (LXR)-mediated hepatocellular steatosis. In Hep3B human hepatoma cells, T0901317 (a specific LXR activator) induced lipid accumulation and this was inhibited by apelin. T0901317 also induced the expression of SREBP-1c, a key transcription factor for lipogenesis. Apelin not only inhibited SREBP-1c induction at the mRNA and protein levels but also induced lipolytic PPARα expression. Furthermore, these protective effects of apelin were inhibited by apelin F13A (a specific APJ antagonist). Furthermore, silencing of APJ by siRNA transfection also inhibited the actions of apelin. Specific inhibitors of cellular signaling components showed inhibition of lipid accumulation by apelin was mediated through Gi/o proteins, AMPK, and SREBP-1c suppression during the early stage and through AMPK, ERKs, and PPARα induction during the late stage. In addition, the protective effect of apelin was confirmed in mouse primary hepatocytes. Our observations suggest apelin-APJ signaling in hepatocytes functions to protect against lipid accumulation in liver through two signaling pathways, that is, via AMPK activation and PPARα induction.
journal_name
Cell Signaljournal_title
Cellular signallingauthors
Huang J,Kang S,Park SJ,Im DSdoi
10.1016/j.cellsig.2017.08.003subject
Has Abstractpub_date
2017-11-01 00:00:00pages
84-94eissn
0898-6568issn
1873-3913pii
S0898-6568(17)30219-Xjournal_volume
39pub_type
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2007.01.019
更新日期:2007-06-01 00:00:00
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journal_title:Cellular signalling
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journal_title:Cellular signalling
pub_type: 杂志文章
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2018.09.016
更新日期:2019-01-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(92)90023-2
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/0898-6568(93)90080-6
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2019.06.007
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2014.12.014
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2013.05.008
更新日期:2013-09-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2015.01.009
更新日期:2015-05-01 00:00:00
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journal_title:Cellular signalling
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doi:10.1016/j.cellsig.2014.02.021
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doi:10.1016/s0898-6568(99)00010-8
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journal_title:Cellular signalling
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journal_title:Cellular signalling
pub_type: 杂志文章
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journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2014.03.030
更新日期:2014-07-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章,评审
doi:10.1016/j.cellsig.2017.01.026
更新日期:2017-07-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2019.109483
更新日期:2020-02-01 00:00:00
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journal_title:Cellular signalling
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doi:10.1016/j.cellsig.2009.07.009
更新日期:2009-11-01 00:00:00
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journal_title:Cellular signalling
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2011.11.002
更新日期:2012-03-01 00:00:00
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journal_title:Cellular signalling
pub_type: 杂志文章
doi:10.1016/j.cellsig.2009.07.003
更新日期:2009-11-01 00:00:00
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pub_type: 杂志文章
doi:10.1016/0898-6568(90)90078-o
更新日期:1990-01-01 00:00:00