New evidence for the role of ceramide in the development of hepatic insulin resistance.
New evidence for the role of ceramide in the development of hepatic insulin resistance.
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神经酰胺在肝胰岛素抵抗发展中作用的新证据。
DOI：
10.1371/journal.pone.0116858
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Chabowski A
中科院分区：
文献类型：
--
作者：
Konstantynowicz-Nowicka K;Harasim E;Baranowski M;Chabowski A
There are few and contradictory data on the role of excessive accumulation of intracellular sphingolipids, particularly ceramides, in the development of hepatic insulin resistance. In our study we assessed accumulated sphingolipid fractions and clarify the mechanisms of hepatic insulin resistance development as well as involvement of fatty acid and ceramide transporters in this process. In culture of primary rat hepatocytes, exposed to high concentration of palmitic acid (0.75mM) during short and prolonged incubation, high performance liquid chromatography was used to assess intra- and extracellular sphingolipid fractions content. Degree of palmitate-induced insulin resistance was estimated by measuring changes in phosphorylation of insulin pathway proteins by western blotting as well as changes in expression of different type of transporters. In our study short and prolonged exposure of primary hepatocytes to palmitic acid resulted in increased intracellular accumulation of ceramide which inhibited insulin signaling pathway. We observed a significant increase in the expression of fatty-acid transport protein (FATP2) and ceramide transfer protein (CERT) what is consistent with enhanced intracellular ceramide content. The content of extracellular ceramide was increased nearly threefold after short and twofold after long incubation period. Expression of microsomal triglyceride transfer protein (MTP) and ATP-binding cassette transporter (ABCA1) was increased significantly mainly after short palmitate incubation. Our data showed that increase in intarcellular ceramide content contributes to the development of hepatic insulin resistance. We suggest pivotal role of transporters in facilitating fatty acid influx (FATP2), accumulation of ceramides (CERT) and export to the media (MTP and ABCA1).
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影响因子：
4.1
作者：
Powell, DJ;Turban, S;Hundal, HS
通讯作者：
Hundal, HS
影响因子：
6.3
作者：
Chabowski, A.;Zendzian-Piotrowska, M.;Gorski, J.
通讯作者：
Gorski, J.
DOI：
10.1073/pnas.1311176110
发表时间：
2013-07-30
影响因子：
11.1
作者：
Galbo, Thomas;Perry, Rachel J.;Shulman, Gerald I.
通讯作者：
Shulman, Gerald I.
DOI：
10.1111/j.1872-034x.2011.00934.x
发表时间：
2012-04
期刊：
Hepatology research : the official journal of the Japan Society of Hepatology
影响因子：
--
作者：
Longato L;Tong M;Wands JR;de la Monte SM
通讯作者：
de la Monte SM
自噬可防止棕榈酸酯诱导的肝细胞凋亡
影响因子：
7.5
作者：
Cai N;Zhao X;Jing Y;Sun K;Jiao S;Chen X;Yang H;Zhou Y;Wei L
通讯作者：
Wei L