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.
Scientists 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 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, authors propose that eIF6 could be a therapeutic target for these diseases.
http://www.nature.com/ncomms/2015/150918/ncomms9261/full/ncomms9261.html
Coupling translation to transcription by eukaryotic initiation factor 6 (eIF6) to regulate insulin sensitivity and lipid metabolism
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