Roles for miRNA-378/378* in adipocyte gene expression and lipogenesis
- 1 August 2010
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Endocrinology and Metabolism
- Vol. 299 (2), E198-E206
- https://doi.org/10.1152/ajpendo.00179.2010
Abstract
In this study, we explored the roles of microRNAs in adipocyte differentiation and metabolism. We first knocked down Argonaute2 (Ago2), a key enzyme in the processing of micro-RNAs (miRNAs), to investigate a potential role for miRNAs in adipocyte differentiation and/or metabolism. Although we did not observe dramatic differences in adipogenesis between Ago2 knock-down and control 3T3-L1 cells, incorporation of [14C]glucose or acetate into triacylglycerol, and steady-state levels of triacyglycerol were all reduced, suggesting a role for miRNAs in adipocyte metabolism. To study roles of specific miRNAs in adipocyte biology, we screened for miRNAs that are differentially expressed between preadipocytes and adipocytes for the 3T3-L1 and ST2 cell lines. Distinct subsets of miRNAs decline or increase during adipocyte conversion, whereas most miRNAs are not regulated. One locus encoding two miRNAs, 378/378*, contained within the intron of PGC-1β is highly induced during adipogenesis. When overexpressed in ST2 mesenchymal precursor cells, miRNA378/378* increases the size of lipid droplets and incorporation of [14C]acetate into triacylglycerol. Although protein and mRNA expression levels of C/EBPα, C/EBPβ, C/EBPδ, and PPARγ1 are unchanged, microarray and quantitative RT-PCR analyses indicate that a set of lipogenic genes are upregulated, perhaps due to increased expression of PPARγ2. Knock-down of miRNA378 and/or miRNA378* decreases accumulation of triacylglycerol. Interestingly, we made the unexpected finding that miRNA378/378* specifically increases transcriptional activity of C/EBPα and C/EBPβ on adipocyte gene promoters.Keywords
This publication has 26 references indexed in Scilit:
- MicroRNA let-7 Regulates 3T3-L1 AdipogenesisMolecular Endocrinology, 2009
- Essential and overlapping functions for mammalian Argonautes in microRNA silencingGenes & Development, 2009
- Human multipotent stromal cells from bone marrow and microRNA: Regulation of differentiation and leukemia inhibitory factor expressionProceedings of the National Academy of Sciences, 2008
- Fat-specific Protein 27 Regulates Storage of TriacylglycerolJournal of Biological Chemistry, 2008
- Effects of Dicer and Argonaute down-regulation on mRNA levels in human HEK293 cellsNucleic Acids Research, 2006
- The colorectal microRNAomeProceedings of the National Academy of Sciences of the United States of America, 2006
- Silencing of microRNAs in vivo with ‘antagomirs’Nature, 2005
- Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profilesProceedings of the National Academy of Sciences of the United States of America, 2005
- Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA TargetsCell, 2005
- PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetesNature Genetics, 2003