MicroRNAs in metabolism and metabolic diseases.
MicroRNAs in metabolism and metabolic diseases.
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DOI：
10.1101/sqb.2011.76.011049
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Näär AM
中科院分区：
文献类型：
--
作者：
Rottiers V;Najafi-Shoushtari SH;Kristo F;Gurumurthy S;Zhong L;Li Y;Cohen DE;Gerszten RE;Bardeesy N;Mostoslavsky R;Näär AM
在发达国家，胆固醇/脂类平衡异常与许多流行疾病有关，包括代谢综合征、II型糖尿病和心血管疾病。我们之前已经发现了固醇调节元件结合蛋白(SREBP)转录因子家族的基因调控机制，这些转录因子控制着与胆固醇和脂质生物合成和摄取相关的基因的表达。有趣的是，我们最近发现了嵌入在人类SREBF基因内含子序列中的保守microRNAs(miR-33a/b)，它与宿主基因产物协同作用，调节胆固醇/脂质稳态。事实上，miR-33a/b控制着ABCA1的水平，ABCA1是一种胆固醇外流泵，对高密度脂蛋白(HDL)的合成和外围组织的胆固醇反向运输至关重要。重要的是，在小鼠中反义抑制miR-33会导致高密度脂蛋白升高和动脉粥样硬化减少。有趣的是，miR-33a/b还通过控制脂肪酸β氧化基因CRORT、HADHB和CPT1a，以及能量传感器AMPK、依赖NAD+的sirtuin SIRT6和胰岛素信号中间产物IRS-2(糖和脂代谢的关键调节因子)，在脂肪酸/脂代谢的动态平衡途径中发挥作用。这些结果揭示了一个高度整合的微RNA-宿主基因电路，它控制着哺乳动物的胆固醇/脂代谢和能量平衡，这可能对心脏代谢障碍的治疗具有重要的治疗意义。
Aberrant cholesterol/lipid homeostasis is linked to a number of diseases prevalent in the developed world including metabolic syndrome, type II diabetes, and cardiovascular disease. We have previously uncovered gene regulatory mechanisms of the Sterol Regulatory Element-Binding Protein (SREBP) family of transcription factors, which control the expression of genes involved in cholesterol and lipid biosynthesis and uptake. Intriguingly, we recently discovered conserved microRNAs (miR-33a/b) embedded within intronic sequences of the human SREBF genes that act in a concerted manner with their host gene products to regulate cholesterol/lipid homeostasis. Indeed, miR-33a/b control the levels of ABCA1, a cholesterol efflux pump critical for high-density lipoprotein (HDL) synthesis and reverse cholesterol transport from peripheral tissues. Importantly, antisense inhibition of miR-33 in mice results in elevated HDL and decreased atherosclerosis. Intriguingly, miR-33a/b also act in the fatty acid/lipid homeostasis pathway by controlling the fatty acid β-oxidation genes CROT, HADHB and CPT1A, as well as the energy sensor AMPK, the NAD+-dependent sirtuin SIRT6, and the insulin signaling intermediate IRS-2, key regulators of glucose and lipid metabolism. These results have revealed a highly integrated microRNA-host gene circuit governing cholesterol/lipid metabolism and energy homeostasis in mammals that may have important therapeutic implications for the treatment of cardiometabolic disorders.
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影响因子：
4.8
作者：
Gerin, Isabelle;Clerbaux, Laure-Alix;Bommer, Guido T.
通讯作者：
Bommer, Guido T.
影响因子：
7.7
作者：
Foretz, M;Ancellin, N;Viollet, B
通讯作者：
Viollet, B
DOI：
10.1073/pnas.0404297101
发表时间：
2004-08-03
影响因子：
11.1
作者：
Chen, GX;Liang, GS;Brown, MS
通讯作者：
Brown, MS
DOI：
10.1196/annals.1320.002
发表时间：
2004-01-01
期刊：
CARNITINE: THE SCIENCE BEHIND A CONDITIONALLY ESSENTIAL NUTRIENT
影响因子：
--
作者：
Jogl, G;Hsiao, YS;Tong, L
通讯作者：
Tong, L
影响因子：
14.9
作者：
Betel D;Wilson M;Gabow A;Marks DS;Sander C
通讯作者：
Sander C