Overexpression of sphingosine kinase 1 prevents ceramide accumulation and ameliorates muscle insulin resistance in high-fat diet-fed mice.
Overexpression of sphingosine kinase 1 prevents ceramide accumulation and ameliorates muscle insulin resistance in high-fat diet-fed mice.
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DOI：
10.2337/db12-0029
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发表时间：
2012-12
期刊：
影响因子：
7.7
通讯作者：
Febbraio MA
中科院分区：
文献类型：
--
作者：
Bruce CR;Risis S;Babb JR;Yang C;Kowalski GM;Selathurai A;Lee-Young RS;Weir JM;Yoshioka K;Takuwa Y;Meikle PJ;Pitson SM;Febbraio MA
鞘脂鞘氨醇-1-磷酸（S1 P）和神经酰胺是具有多种细胞效应的重要生物活性脂质。细胞内神经酰胺积累导致胰岛素抵抗，但鞘氨醇激酶1（SphK 1）阻止神经酰胺积累，部分是通过促进其代谢为S1 P。尽管如此，SphK 1在调节胰岛素作用中的作用在很大程度上被忽视了。过表达SphK 1的转基因（Tg）小鼠在进行几项代谢分析之前，喂食标准食物或高脂饮食（HFD）6周。与野生型（WT）同窝仔相比，喂食HFD的SphK 1 Tg小鼠骨骼肌中SphK活性增加，这与肌内神经酰胺蓄积减弱有关。这与c-jun氨基末端激酶（一种与胰岛素抵抗相关的丝氨酸/苏氨酸激酶）磷酸化水平的降低有关。因此，与WT小鼠相比，当喂食HFD时，SphK 1 Tg小鼠的骨骼肌和全身胰岛素敏感性得到改善。我们已经确定，SphK 1酶是一个重要的调节器的脂质分配和胰岛素作用在骨骼肌的条件下，增加脂质供应。
The sphingolipids sphingosine-1-phosphate (S1P) and ceramide are important bioactive lipids with many cellular effects. Intracellular ceramide accumulation causes insulin resistance, but sphingosine kinase 1 (SphK1) prevents ceramide accumulation, in part, by promoting its metabolism into S1P. Despite this, the role of SphK1 in regulating insulin action has been largely overlooked. Transgenic (Tg) mice that overexpress SphK1 were fed a standard chow or high-fat diet (HFD) for 6 weeks before undergoing several metabolic analyses. SphK1 Tg mice fed an HFD displayed increased SphK activity in skeletal muscle, which was associated with an attenuated intramuscular ceramide accumulation compared with wild-type (WT) littermates. This was associated with a concomitant reduction in the phosphorylation of c-jun amino-terminal kinase, a serine threonine kinase associated with insulin resistance. Accordingly, skeletal muscle and whole-body insulin sensitivity were improved in SphK1 Tg, compared with WT mice, when fed an HFD. We have identified that the enzyme SphK1 is an important regulator of lipid partitioning and insulin action in skeletal muscle under conditions of increased lipid supply.
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影响因子：
64.8
作者：
Fu, Suneng;Yang, Ling;Li, Ping;Hofmann, Oliver;Dicker, Lee;Hide, Winston;Lin, Xihong;Watkins, Steven M.;Ivanov, Alexander R.;Hotamisligil, Goekhan S.
通讯作者：
Hotamisligil, Goekhan S.
影响因子：
4.8
作者：
Di, Anke;Kawamura, Takeshi;Malik, Asrar B.
通讯作者：
Malik, Asrar B.
影响因子：
29
作者：
Holland, William L.;Brozinick, Joseph T.;Summers, Scott A.
通讯作者：
Summers, Scott A.
DOI：
10.1016/j.bbrc.2004.10.036
发表时间：
2004-12-03
影响因子：
3.1
作者：
Ikeda, M;Kihara, A;Igarashi, Y
通讯作者：
Igarashi, Y
影响因子：
4.7
作者：
Edsall, LC;Cuvillier, O;Milstien, S
通讯作者：
Milstien, S