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

Cell Rep. 2015 Oct 13;13(2):350-64. Epub 2015 Oct 01

Jaakko Mattila ¹ , Essi Havula ¹ , Erja Suominen ¹ , Mari Teesalu ¹ , Ida Surakka ² ,

Jaakko Mattila ¹ , Essi Havula ¹ , Erja Suominen ¹ , Mari Teesalu ¹ , Ida Surakka ² , Riikka Hynynen ¹ , Helena Kilpinen ³ , Juho Väänänen ⁴ , Iiris Hovatta ⁵ , Reijo Käkelä ⁴ , Samuli Ripatti ⁶ , Thomas Sandmann ⁷ , Ville Hietakangas ⁸

+ et al

Author information

¹ Department of Biosciences, University of Helsinki, Helsinki 00790, Finland; Institute of Biotechnology, University of Helsinki, Helsinki 00790, Finland.
² Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00270, Finland; Department of Health, National Institute for Health and Welfare, Helsinki 00251, Finland.
³ EMBL-EBI, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
⁴ Department of Biosciences, University of Helsinki, Helsinki 00790, Finland.
⁵ Department of Biosciences, University of Helsinki, Helsinki 00790, Finland; Department of Health, National Institute for Health and Welfare, Helsinki 00251, Finland.
⁶ Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00270, Finland; Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki 00251, Finland; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
⁷ Department of Bioinformatics and Computational Biology, Genentech Inc., South San Francisco, CA 94080, USA.
⁸ Department of Biosciences, University of Helsinki, Helsinki 00790, Finland; Institute of Biotechnology, University of Helsinki, Helsinki 00790, Finland. Electronic address: ville.hietakangas@helsinki.fi.

摘要

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.

原始数据

保存测序数据

Sample name	Organism	Experiment title	Sample type	Library instrument	Attributes
Sample name	Organism	Experiment title	Sample type	Library instrument	development stage	genotype	source name	tissue
control HSD 8h repC	Drosophila melanogaster	GSM1824688: control HSD 8h repC; Drosophila melanogaster; RNA-Seq	RNA-Seq	NextSeq 500	3rd instar	sug17delta/+	control heterozygous (sug17d/+) 3rd instar high sugar diet	whole larvae
sug HSD 8h repC	Drosophila melanogaster	GSM1824687: sug HSD 8h repC; Drosophila melanogaster; RNA-Seq	RNA-Seq	NextSeq 500	3rd instar	sug17delta/Df(2R)Exel7123	sugarbabe null mutant (sug17d/sug def) 3rd instar high sugar diet	whole larvae
control LSD 1.5h repC	Drosophila melanogaster	GSM1824686: control LSD 1.5h repC; Drosophila melanogaster; RNA-Seq	RNA-Seq	NextSeq 500	3rd instar	sug17delta/+	control heterozygous (sug17d/+) 3rd instar control diet	whole larvae
sug LSD 1.5h repC	Drosophila melanogaster	GSM1824685: sug LSD 1.5h repC; Drosophila melanogaster; RNA-Seq	RNA-Seq	NextSeq 500	3rd instar	sug17delta/Df(2R)Exel7123	sugarbabe null mutant (sug17d/sug def) 3rd instar control diet	whole larvae
control HSD 8h repB	Drosophila melanogaster	GSM1824684: control HSD 8h repB; Drosophila melanogaster; RNA-Seq	RNA-Seq	NextSeq 500	3rd instar	sug17delta/+	control heterozygous (sug17d/+) 3rd instar high sugar diet	whole larvae