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

• DOI: 10.1038/ncomms9261
• Publication Date: 2015-09-18T11:04:28Z
• Authors: Daniela Brina; Annarita Miluzio; Sara Ricciardi; Kim Clarke; Peter K. Davidsen; Gabriella Viero; Toma Tebaldi; Nina Offenhäuser; Jan Rozman; Birgit Rathkolb; Susanne Neschen; Martin Klingenspor; Eckhard Wolf; Valerie Gailus-Du...; Helmut Fuchs; Martin Hrabe de A...; Alessandro Quattrone; Francesco Falciani; Stefano Biffo
• Keywords: Lipogenesis; Fatty acid synthesis

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 is unknown. Here we show that reduction mice heterozygous for eIF6 results normal but less blood cholesterol triglycerides. controls fatty acid synthesis glycolysis a cell autonomous fashion. acts by exerting translational control adipogenic transcription factors like C/EBPβ, C/EBPδ ATF4 have G/C rich or uORF sequences their 5′ UTR. outcome the activation reshaping gene expression increased levels lipogenic glycolytic enzymes. Finally, modulate histone acetylation amounts rate-limiting synthase (Fasn) mRNA. Since obesity, type 2 diabetes, cancer require Fasn-driven state, propose could be therapeutic target these diseases.