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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Iliopoulos, Dimitrios Drosatos, Konstantinos Hiyama, Yaeko Goldberg, Ira J. Zannis, Vassilis I. |
| Description | Country affiliation: United States Author Affiliation: Iliopoulos D ( Department of Biological Chemistry and Molecular Pharmacology, School of Medicine, Harvard University, Boston, MA, USA.) |
| Abstract | We previously observed that treatment of mice with a dominant negative form of cJun (dn-cJun) increased the expression of genes involved in lipid metabolism and modulated the expression of nine microRNAs (miR). To investigate the potential effect of these miRs on the expression of the genes of lipid metabolism, we performed studies in cultured HepG2 cells. Transfection of HepG2 cells with sense or antisense miR-370 or miR-122 upregulated and downregulated, respectively, the transcription factor sterol-regulatory element binding protein 1c (SREBP-1c) and the enzymes diacylglycerol acyltransferase-2 (DGAT2), fatty acid synthase (FAS), and acyl-CoA carboxylase 1 (ACC1) that regulate fatty acid and triglyceride biosynthesis. The other seven miRs identified by the miR array screening did not affect the expression of lipogenic genes. miR-370 upregulated the expression of miR-122. Furthermore, the effect of miR-370 on the expression of the lipogenic genes was abolished by antisense miR-122. miR-370 targets the 3' untranslated region (UTR) of Cpt1alpha, and it downregulated the expression of the carnitine palmitoyl transferase 1alpha (Cpt1alpha) gene as well as the rate of beta oxidation. Our data suggest that miR-370 acting via miR-122 may have a causative role in the accumulation of hepatic triglycerides by modulating initially the expression of SREBP-1c, DGAT2, and Cpt1alpha and, subsequently, the expression of other genes that affect lipid metabolism. |
| File Format | HTM / HTML |
| ISSN | 00222275 |
| e-ISSN | 15397262 |
| DOI | 10.1194/jlr.M004812 |
| Journal | The Journal of Lipid Research |
| Issue Number | 6 |
| Volume Number | 51 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology |
| Publisher Date | 2010-06-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Discipline Biochemistry Carnitine O-palmitoyltransferase Genetics Gene Expression Regulation Lipid Metabolism Micrornas Metabolism 3' Untranslated Regions Acetyltransferases Adenoviridae Animals Antigens, Cd95 Cell Line, Tumor Computational Biology Diacylglycerol O-acyltransferase Down-regulation Extracellular Space Fatty Acids Genes, Jun Lipogenesis Liver Mice Molecular Sequence Data Oxidation-reduction Sterol Regulatory Element Binding Protein 1 Triglycerides Up-regulation Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Endocrinology |
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