miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling Journal Article
| Authors: | Dávalos, A.; Goedeke, L.; Smibert, P.; Ramirez, C. M.; Warrier, N. P.; Andreo, U.; Cirera-Salinas, D.; Rayner, K.; Suresh, U.; Pastor-Pareja, J. C.; Esplugues, E.; Fisher, E. A.; Penalva, L. O. F.; Moore, K. J.; Suarez, Y.; Lai, E. C.; Fernández-Hernando, C. |
| Article Title: | miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling |
| Abstract: | Cellular imbalances of cholesterol and fatty acid metabolism result in pathological processes, including atherosclerosis and metabolic syndrome. Recent work from our group and others has shown that the intronic microRNAs hsa-miR-33a and hsa-miR-33b are located within the sterol regulatory element-binding protein-2 and -1 genes, respectively, and regulate cholesterol homeostasis in concert with their host genes. Here, we show that miR-33a and -b also regulate genes involved in fatty acid metabolism and insulin signaling. miR-33a and -b target key enzymes involved in the regulation of fatty acid oxidation, including carnitine O-octaniltransferase, carnitine palmitoyltransferase 1A, hydroxyacyl-CoA-dehydrogenase, Sirtuin 6 (SIRT6), and AMP kinase subunit-α. Moreover, miR-33a and -b also target the insulin receptor substrate 2, an essential component of the insulin-signaling pathway in the liver. Overexpression of miR-33a and -b reduces both fatty acid oxidation and insulin signaling in hepatic cell lines, whereas inhibition of endogenous miR-33a and -b increases these two metabolic pathways. Together, these data establish that miR-33a and -b regulate pathways controlling three of the risk factors of metabolic syndrome, namely levels of HDL, triglycerides, and insulin signaling, and suggest that inhibitors of miR-33a and -b may be useful in the treatment of this growing health concern. |
| Keywords: | signal transduction; unclassified drug; human cell; nonhuman; gene overexpression; microrna; liver; transcription regulation; cardiovascular disease; adenylate kinase; insulin; triacylglycerol; liver cell; metabolic disorder; posttranscriptional regulation; acyltransferase; lipid homeostasis; 3 hydroxyacyl coenzyme a dehydrogenase; adenylate kinase alpha; carnitine o octaniltransferase; carnitine palmitoyltransferase 1a; high density lipoprotein; insulin receptor substrate 2; mir 33a; mir 33b; sirtuin 6; fatty acid metabolism; fatty acid oxidation |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 108 |
| Issue: | 22 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2011-05-31 |
| Start Page: | 9232 |
| End Page: | 9237 |
| Language: | English |
| DOI: | 10.1073/pnas.1102281108 |
| PROVIDER: | scopus |
| PMCID: | PMC3107310 |
| PUBMED: | 21576456 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 17 August 2011" - "CODEN: PNASA" - "Source: Scopus" |
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