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eIF6 coordinates insulin sensitivity and lipid metabolism by coupling translation to transcription.

Abstract：

: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/EBPβ, C/EBPδ 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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Brina D,Miluzio A,Ricciardi S,Clarke K,Davidsen PK,Viero G,Tebaldi T,Offenhäuser 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

doi

10.1038/ncomms9261

subject

Has Abstract

pub_date

2015-09-18 00:00:00

pages

8261

issn

2041-1723

pii

ncomms9261

journal_volume

6

pub_type

杂志文章

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