MiR-155 has a protective role in the development of non-alcoholic hepatosteatosis in mice.
MiR-155 has a protective role in the development of non-alcoholic hepatosteatosis in mice.
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DOI：
10.1371/journal.pone.0072324
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Kurowska-Stolarska M
中科院分区：
文献类型：
--
作者：
Miller AM;Gilchrist DS;Nijjar J;Araldi E;Ramirez CM;Lavery CA;Fernández-Hernando C;McInnes IB;Kurowska-Stolarska M
肝脂肪变性是一种全球流行病，被认为是2型糖尿病的发病机制。microRNA（miRs）是一种调节因子，可以在肝脏中整合一系列代谢和炎症途径。我们的目的是研究miR-155在肝脂肪变性中的功能作用。雄性C57 BL/6野生型（WT）和miR-155−/−小鼠喂食正常食物或高脂饮食（HFD）6个月，然后评估小鼠肝脏和血清中的脂质水平、代谢和炎症参数。与WT对照相比，喂食HFD 6个月的缺乏内源性miR-155的小鼠发生了增加的肝脂肪变性。这与肝脏重量和血清VLDL/LDL胆固醇和丙氨酸转氨酶（ALT）水平增加，以及参与葡萄糖调节（Pck 1，Cebpa），脂肪酸摄取（Cd 36）和脂质代谢（Fasn，Fabp 4，Lpl，Abcd 2，Pla 2g 7）的基因的肝脏表达增加有关。使用miRNA靶点预测算法和miR-155−/−肝脏的微阵列转录组学图谱，我们确定并验证了Nr 1h 3（LXRα）作为直接miR-155靶基因，可能与miR-155−/−小鼠的肝脏表型有关。总之，这些数据表明，miR-155在调节肝脏中的脂质代谢中起着关键作用，并且其失调可能导致糖尿病患者的肝脂肪变性。
Hepatic steatosis is a global epidemic that is thought to contribute to the pathogenesis of type 2 diabetes. MicroRNAs (miRs) are regulators that can functionally integrate a range of metabolic and inflammatory pathways in liver. We aimed to investigate the functional role of miR-155 in hepatic steatosis. Male C57BL/6 wild-type (WT) and miR-155−/− mice were fed either normal chow or high fat diet (HFD) for 6 months then lipid levels, metabolic and inflammatory parameters were assessed in livers and serum of the mice. Mice lacking endogenous miR-155 that were fed HFD for 6 months developed increased hepatic steatosis compared to WT controls. This was associated with increased liver weight and serum VLDL/LDL cholesterol and alanine transaminase (ALT) levels, as well as increased hepatic expression of genes involved in glucose regulation (Pck1, Cebpa), fatty acid uptake (Cd36) and lipid metabolism (Fasn, Fabp4, Lpl, Abcd2, Pla2g7). Using miRNA target prediction algorithms and the microarray transcriptomic profile of miR-155−/− livers, we identified and validated that Nr1h3 (LXRα) as a direct miR-155 target gene that is potentially responsible for the liver phenotype of miR-155−/− mice. Together these data indicate that miR-155 plays a pivotal role regulating lipid metabolism in liver and that its deregulation may lead to hepatic steatosis in patients with diabetes.
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DOI：
10.1038/labinvest.2010.113
发表时间：
2010-10
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
--
作者：
通讯作者：
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影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
CERNA假设：隐藏RNA语言的Rosetta石头？
影响因子：
64.5
作者：
Salmena L;Poliseno L;Tay Y;Kats L;Pandolfi PP
通讯作者：
Pandolfi PP
影响因子：
3.7
作者：
Donners MM;Wolfs IM;Stöger LJ;van der Vorst EP;Pöttgens CC;Heymans S;Schroen B;Gijbels MJ;de Winther MP
通讯作者：
de Winther MP
人类脂肪肝病：旧问题和新见解。
DOI：
10.1126/science.1204265
发表时间：
2011-06-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cohen JC;Horton JD;Hobbs HH
通讯作者：
Hobbs HH