AutoriBrina D.; Miluzio A.; Ricciardi S.; Clarke K.; Davidsen P.K.; Viero G.; Tebaldi T.; Offenhauser N.; Rozman J.; Rathkolb B.; Neschen S.; Klingenspor M.; Wolf E.; Gailus-Durner V.; Fuchs H.; Hrabe De Angelis M.; Quattrone A.; Falciani F.; Biffo S.
AbstractInsulin 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/EBP?, C/EBP? 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.
RivistaNature Communications
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Autori IBFGabriella VIERO
Linee di Ricerca IBFMD.P01.028.001