期刊
CELL REPORTS
卷 13, 期 2, 页码 350-364出版社
CELL PRESS
DOI: 10.1016/j.celrep.2015.08.081
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资金
- European Research Council [281720]
- Sigrid Juselius Foundation
- Novo Nordisk Foundation
- Biocentrum Helsinki
- Academy of Finland [137530]
- Integrative Life Science Doctoral Program
- Finnish Diabetes Research Foundation
- Emil Aaltonen Foundation
- Biomedicum Helsinki Foundation
- Maud Kuistila Foundation
- Jenny and Antti Wihuri Foundation
- Novo Nordisk Fonden [NNF14OC0010729] Funding Source: researchfish
- European Research Council (ERC) [281720] Funding Source: European Research Council (ERC)
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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