Department of Biosciences, University of Helsinki, Helsinki 00790, Finland; Institute of Biotechnology, University of Helsinki, Helsinki 00790, Finland.
Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00270, Finland; Department of Health, National Institute for Health and Welfare, Helsinki 00251, Finland.
Cell Rep. 2015 Oct 13;13(2):350-64. doi: 10.1016/j.celrep.2015.08.081. Epub 2015 Oct 1.
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.
ChREBP/Mondo-Mlx 转录因子被糖激活，是糖耐受所必需的。它们促进糖向脂质的转化，但除此之外，它们的生理作用还不够了解。在这里，我们证明在果蝇的全器官水平上，Mondo-Mlx 控制了大多数与营养消化和运输以及碳水化合物、氨基酸和脂质代谢有关的糖调节基因。此外，Mondo-Mlx 靶标的人类同源物在与高循环甘油三酯相关的基因变异体中富集。除了对代谢基因的直接调控外，Mondo-Mlx 通过下游效应物，包括激活素配体 Dawdle 和 Gli 类似转录因子 Sugarbabe，维持代谢稳态。Sugarbabe 控制了一组依赖于 Mondo-Mlx 的过程，包括从头脂肪生成和脂肪酸去饱和。总之，Mondo-Mlx 是其他糖反应途径的主要调节剂，这些途径对于适应高糖饮食是必不可少的。
