Role of miR-181c in Diet-induced obesity through regulation of lipid synthesis in liver.
Role of miR-181c in Diet-induced obesity through regulation of lipid synthesis in liver.
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DOI：
10.1371/journal.pone.0256973
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Das S
中科院分区：
文献类型：
--
作者：
Akiyoshi K;Boersma GJ;Johnson MD;Velasquez FC;Dunkerly-Eyring B;O'Brien S;Yamaguchi A;Steenbergen C;Tamashiro KLK;Das S
我们最近在心肌细胞中发现了一种核编码的miRNA（miR-181 c），它可以转位到线粒体中调节线粒体基因mt-COX 1，并通过线粒体途径影响肥胖诱导的心功能障碍。由于肝脏在肥胖过程中起着关键作用，我们假设miR-181 c可能有助于与肥胖相关的病理生理并发症。因此，我们使用miR-181 c/d-/-小鼠来研究miR-181 c在饮食诱导的肥胖期间肝细胞脂肪生成中的作用。小鼠被喂食高脂肪（HF）饮食26周，在此期间进行间接热量测量。使用定量PCR（qPCR）来检查参与脂质合成的基因的表达。我们发现，miR-181 c/d-/-小鼠并没有受到HF暴露的所有代谢后果的保护。26周后，miR-181 c/d-/-小鼠的体脂百分比显著高于野生型（WT）小鼠。葡萄糖耐量试验显示高胰岛素血症和高血糖症，表明miR-181 c/d-/-小鼠的胰岛素不敏感性。喂食HF饲料的miR-181 c/d-/-小鼠的血清和肝脏甘油三酯水平高于喂食相同饲料的WT小鼠。qPCR数据显示，由异柠檬酸脱氢酶1（IDH 1）调节的几个基因在miR-181 c/d-/-肝脏中的上调程度高于WT肝脏。此外，通过腺相关病毒体内递送的miR-181 c通过下调肝脏中这些相同的脂质合成基因来减弱脂肪生成。在肝细胞中，miR-181 c通过靶向IDH 1调节脂质生物合成。总之，数据表明miR-181 c的过表达可以有益于各种脂质代谢紊乱。
We recently identified a nuclear-encoded miRNA (miR-181c) in cardiomyocytes that can translocate into mitochondria to regulate mitochondrial gene mt-COX1 and influence obesity-induced cardiac dysfunction through the mitochondrial pathway. Because liver plays a pivotal role during obesity, we hypothesized that miR-181c might contribute to the pathophysiological complications associated with obesity. Therefore, we used miR-181c/d-/- mice to study the role of miR-181c in hepatocyte lipogenesis during diet-induced obesity. The mice were fed a high-fat (HF) diet for 26 weeks, during which indirect calorimetric measurements were made. Quantitative PCR (qPCR) was used to examine the expression of genes involved in lipid synthesis. We found that miR-181c/d-/- mice were not protected against all metabolic consequences of HF exposure. After 26 weeks, the miR-181c/d-/- mice had a significantly higher body fat percentage than did wild-type (WT) mice. Glucose tolerance tests showed hyperinsulinemia and hyperglycemia, indicative of insulin insensitivity in the miR-181c/d-/- mice. miR-181c/d-/- mice fed the HF diet had higher serum and liver triglyceride levels than did WT mice fed the same diet. qPCR data showed that several genes regulated by isocitrate dehydrogenase 1 (IDH1) were more upregulated in miR-181c/d-/- liver than in WT liver. Furthermore, miR-181c delivered in vivo via adeno-associated virus attenuated the lipogenesis by downregulating these same lipid synthesis genes in the liver. In hepatocytes, miR-181c regulates lipid biosynthesis by targeting IDH1. Taken together, the data indicate that overexpression of miR-181c can be beneficial for various lipid metabolism disorders.
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DOI：
10.1126/science.1189123
发表时间：
2010-06-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Najafi-Shoushtari SH;Kristo F;Li Y;Shioda T;Cohen DE;Gerszten RE;Näär AM
通讯作者：
Näär AM
影响因子：
8.1
作者：
Martin SD;Morrison S;Konstantopoulos N;McGee SL
通讯作者：
McGee SL
MiR-181a 通过 IDH1 调节脂质代谢
影响因子：
4.6
作者：
Chu B;Wu T;Miao L;Mei Y;Wu M
通讯作者：
Wu M
影响因子：
64.8
作者：
Metallo, Christian M.;Gameiro, Paulo A.;Bell, Eric L.;Mattaini, Katherine R.;Yang, Juanjuan;Hiller, Karsten;Jewell, Christopher M.;Johnson, Zachary R.;Irvine, Darrell J.;Guarente, Leonard;Kelleher, Joanne K.;Vander Heiden, Matthew G.;Iliopoulos, Othon;Stephanopoulos, Gregory
通讯作者：
Stephanopoulos, Gregory
影响因子：
37.8
作者：
Alberti, K. G. M. M.;Eckel, Robert H.;Smith, Sidney C., Jr.
通讯作者：
Smith, Sidney C., Jr.