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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GLIS3: A novel transcriptional regulator of mitochondrial functions and metabolic reprogramming in postnatal kidney and polycystic kidney disease.
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Cell Biology Group, Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, 27709, USA. Electronic address:
Objectives: Deficiency in the transcription factor (TF) GLI-Similar 3 (GLIS3) in humans and mice leads to the development of polycystic kidney disease (PKD). In this study, we investigate the role of GLIS3 in the regulation of energy metabolism and mitochondrial functions in relation to its role in normal kidney and metabolic reprogramming in PKD pathogenesis.
Methods: Transcriptomics, cistromics, and metabolomics were used to obtain insights into the role of GLIS3 in the regulation of energy homeostasis and mitochondrial metabolism in normal kidney and PKD pathogenesis using GLIS3-deficient mice.
The IL-1β/STAT1 Axis inhibits STAT3 function via Sequestration of the transcriptional activator GLIS2, leading to postoperative vascular dysfunction.
Int Immunopharmacol
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Department of Anesthesiology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, China. Electronic address:
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Islets
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Department of Biological Sciences, Murray State University, Murray, KY, USA.
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Cell Biology Section, Immunity, Inflammation and Disease Laboratory, Research Triangle Park, NC, 27709, USA.
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View Article and Find Full Text PDFAn Insight into the Role of GLIS1 in Embryonic Development, iPSC Generation, and Cancer.
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Laboratory for Stem Cell Engineering and Regenerative Medicine, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, India.
The curiosity to discover transcription factors to reprogram somatic cells to induced pluripotent stem cells (iPSCs) resulted in the identification of a reprogramming factor, Gli-similar transcription factor GLIS1. This proline-rich Kruppel-like zinc finger transcription factor has a role in embryonic development, iPSC generation, and cancer. The spatial and temporal expression of GLIS1 during embryonic development implicates that it can control gene expression at specific developmental stages.
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