Mondo-Mlx Mediates Organismal Sugar Sensing through the Gli-Similar Transcription Factor Sugarbabe

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Mattila , J , Havula , E , Suominen , E , Teesalu , M , Surakka , I , Hynynen , R , Kilpinen , H , Vaananen , J , Hovatta , I , Kakela , R , Ripatti , S , Sandmann , T & Hietakangas , V 2015 , ' Mondo-Mlx Mediates Organismal Sugar Sensing through the Gli-Similar Transcription Factor Sugarbabe ' , Cell Reports , vol. 13 , no. 2 , pp. 350-364 . https://doi.org/10.1016/j.celrep.2015.08.081

Title: Mondo-Mlx Mediates Organismal Sugar Sensing through the Gli-Similar Transcription Factor Sugarbabe
Author: Mattila, Jaakko; Havula, Essi; Suominen, Erja; Teesalu, Mari; Surakka, Ida; Hynynen, Riikka; Kilpinen, Helena; Vaananen, Juho; Hovatta, Iiris; Kakela, Reijo; Ripatti, Samuli; Sandmann, Thomas; Hietakangas, Ville
Other contributor: University of Helsinki, Institute of Biotechnology
University of Helsinki, Biosciences
University of Helsinki, Biosciences
University of Helsinki, Biosciences
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, United Kingdom
University of Helsinki, Biosciences
University of Helsinki, Biosciences
University of Helsinki, Biosciences
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Biosciences










Date: 2015-10-13
Language: eng
Number of pages: 15
Belongs to series: Cell Reports
ISSN: 2211-1247
DOI: https://doi.org/10.1016/j.celrep.2015.08.081
URI: http://hdl.handle.net/10138/165448
Abstract: The ChREBP/Mondo-Mlx transcription factors are activated by sugars and are essential for sugar tolerance. They promote the conversion of sugars to lipids, but beyond this, their physiological roles are insufficiently understood. Here, we demonstrate that in an organism-wide setting in Drosophila, Mondo-Mlx controls the majority of sugar-regulated genes involved in nutrient digestion and transport as well as carbohydrate, amino acid, and lipid metabolism. Furthermore, human orthologs of the Mondo-Mlx targets display enrichment among gene variants associated with high circulating triglycerides. In addition to direct regulation of metabolic genes, Mondo-Mlx maintains metabolic homeostasis through downstream effectors, including the Activin ligand Dawdle and the Gli-similar transcription factor Sugarbabe. Sugarbabe controls a subset of Mondo-Mlx-dependent processes, including de novo lipogenesis and fatty acid desaturation. In sum, Mondo-Mlx is a master regulator of other sugar-responsive pathways essential for adaptation to a high-sugar diet.
Subject: FATTY LIVER-DISEASE
CENTER-DOT-MLX
DROSOPHILA-MELANOGASTER
PLASMA TRIGLYCERIDES
HEPATIC STEATOSIS
GENE-EXPRESSION
GLUCOSE-METABOLISM
INSULIN-RESISTANCE
AXON GUIDANCE
CHREBP
1182 Biochemistry, cell and molecular biology
3111 Biomedicine
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