| First Author | Brina D | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 8261 | PubMed ID | 26383020 |
| Mgi Jnum | J:226984 | Mgi Id | MGI:5699484 |
| Doi | 10.1038/ncomms9261 | Citation | Brina D, et al. (2015) eIF6 coordinates insulin sensitivity and lipid metabolism by coupling translation to transcription. Nat Commun 6:8261 |
| abstractText | Insulin regulates glycaemia, lipogenesis and increases mRNA translation. Cells with reduced eukaryotic initiation factor 6 (eIF6) do not increase translation in response to insulin. The role of insulin-regulated translation is unknown. Here we show that reduction of insulin-regulated translation in mice heterozygous for eIF6 results in normal glycaemia, but less blood cholesterol and triglycerides. eIF6 controls fatty acid synthesis and glycolysis in a cell autonomous fashion. eIF6 acts by exerting translational control of adipogenic transcription factors like C/EBPbeta, C/EBPdelta and ATF4 that have G/C rich or uORF sequences in their 5' UTR. The outcome of the translational activation by eIF6 is a reshaping of gene expression with increased levels of lipogenic and glycolytic enzymes. Finally, eIF6 levels modulate histone acetylation and amounts of rate-limiting fatty acid synthase (Fasn) mRNA. Since obesity, type 2 diabetes, and cancer require a Fasn-driven lipogenic state, we propose that eIF6 could be a therapeutic target for these diseases. |
