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

Jaakko Mattila | Zendy; Essi Havula | Zendy; Erja Suominen | Zendy; Mari Teesalu | Zendy; Ida Surakka | Zendy; Riikka Hynynen | Zendy; Helena Kilpinen | Zendy; Juho Väänänen | Zendy; Iiris Hovatta | Zendy; Reijo Käkelä | Zendy; Samuli Ripatti | Zendy; Thomas Sandmann | Zendy; Ville Hietakangas | Zendy

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

Author(s) -

Jaakko Mattila,

Essi Havula,

Erja Suominen,

Mari Teesalu,

Ida Surakka,

Riikka Hynynen,

Helena Kilpinen,

Juho Väänänen,

Iiris Hovatta,

Reijo Käkelä,

Samuli Ripatti,

Thomas Sandmann,

Ville Hietakangas

Publication year - 2015

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2015.08.081

Subject(s) - transcription factor , sugar , carbohydrate responsive element binding protein , lipogenesis , gene , chemistry , biochemistry , microbiology and biotechnology , biology

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.

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