MondoA/ChREBP: the usual suspects of transcriptional glucose sensing; Implication in pathophysiology

• Published in: Metabolism, clinical and experimental Vol. 70; pp. 133 - 151
• Main Authors: Richards, Paul, Ourabah, Sarah, Montagne, Jacques, Burnol, Anne-Françoise, Postic, Catherine, Guilmeau, Sandra
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2017
• Subjects: Animals; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism; Cancer; ChREBP; Diabetes; Endocrinology & Metabolism; Energy Metabolism - physiology; Glucose - metabolism; Glucose and lipid metabolism; Glycolysis; Humans; Lipogenesis; MondoA; Transcription Factors - physiology; GWAS; Gck, GK; ENO1; pancreatic and duodenal homeobox 1; PPAR; PI3K; HNF4; GFAT1; glycogen synthase; saturated fatty acids; AcAc; MondoA; glucose phosphate isomerase; ARRDC4; fructose-2,6-bisphosphate; G6PC; carbohydrate responsive element binding protein; nicotinamide adenine dinucleotide phosphate; electrophoretic mobility shift assays; fructokinase; mTOR Complex 2; ACLY; alcoholic liver disease; tricarboxylic acid cycle; G6Pase; fatty acid synthase; PAHSAs; peroxisome proliferator-activated receptorγ coactivator beta; very low-density lipoprotein; SMRT; 3βHB; phosphoinositide 3-kinase; phosphatase 2A; PFKFB3; white adipose tissue; arrestin domain containing 4; FLII; glucose response conserved element; LXR; MUFA; bHLH-LZ; carbohydrate responsive element; alcohol dehydrogenase; nuclear localization signal; liver receptor homolog 1; cAMP; HIF1; SFA; enolase 1; LDHA; mammalian target of rapamycin; NLS; hypoxia-inducible factor 1; PGK1; palmitic acid-hydroxy stearic acids; THR; G6P; Scd1, SCD1; PDHA1; LID; IGF2; PGC-1β; USF; Mlxpil, ChREBP; PP2A; Txnip, TxNIP; DAG; triglycerides; MAFA; NASH; SREBP-1c; transcription factor-like 4; glucose/insulin response element; type 2 diabetes; TG; cyclic adenosine monophosphate; silencing mediator of retinoid and thyroid hormone receptors; glucose and lipid metabolism; glucose-sensing module; TAD; ALD; HAT; diabetes; NES; fructose-6-phosphate; stearoyl CoA desaturase 1; GPI; liver-pyruvate kinase; ADH; Diacylglycerol; v-Maf avian musculoaponeurotic fibrosarcoma oncogene homolog A; HK2; KHK; genome-wide associated studies; glucose 6 phosphatase; phosphoglycerate kinase 1; thyroid receptor; GRACE; VLDL; HBP; mTOR; MLX; lactate deshydrogenase A; CREB binding protein; pyruvate deshydrogenase alpha 1; liver X receptor; upstream stimulating factor; fatty acid elongase; F2,6P 2; glucose 6-phosphatase catalytic subunit; F6P; DCD; G6PDH; PKA; T2D; HCC; ELOVL6; monounsaturated fatty acids; EMT; ER; epithelial-to-mesenchymal transition; histone acetyl-transferase; Xu5P; non alcoholic fatty liver disease; GIRE; ROS; dimerization and cytoplasmic localization domain; xylulose 5-phosphate; insulin-like growth factor 2; mTORC2; FoxO1; Pklr, L-PK; Max-like protein X; non-alcoholic steatohepatitis; ribosomal protein S14; NADPH; FXR; PTG; glycogen-targeting protein; NAFLD; peroxisome proliferator-activated receptors; ATP citrate lyase; Basic-helix–loop-helix leucine zipper; glucose 6 phosphate dehydrogenase; thioredoxin-interacting protein; WAT; chicken ovalbumin upstream promoter-transcription factor II; flightless II; protein kinase; hepatocellular carcinomas; CBP; nicotinamide adenine dinucleotide; deoxyribonucleic acid; 6-phosphofructo-2-kinase; EMSA; hepatocyte nuclear factor 4; reactive oxygen species; ChoRE; glutamine:fructose-6-phosphate amino-transferase; GSM; TCFL4; sterol regulatory element binding protein; COUP-TFII; estrogen receptor; farnesoid X receptor; hexokinase 2; TCA cycle; VEGF; PDX1; transactivation domain; Acaca, ACC; nuclear export signal; WBS; 3-β-hydroxybutyrate; Fasn, FAS; fork head box 1; GS; Rps14, S14; low glucose inhibitory domain; hexosamine biosynthesis pathway; NAD; ChREBP; acetoacetate; LRH-1; DNA; vascular endothelial growth factor; Williams-Beuren syndrome; glucose 6-phosphate; cancer; cetyl-CoA carboxylase; glucokinase; Glucose and lipid metabolism; Diabetes; Cancer
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2017.01.033

Abstract Identification of the Mondo glucose-responsive transcription factors family, including the MondoA and MondoB/ChREBP paralogs, has shed light on the mechanism whereby glucose affects gene transcription. They have clearly emerged, in recent years, as key mediators of glucose sensing by multiple cell types. MondoA and ChREBP have overlapping yet distinct expression profiles, which underlie their downstream targets and separate roles in regulating genes involved in glucose metabolism. MondoA can restrict glucose uptake and influences energy utilization in skeletal muscle, while ChREBP signals energy storage through de novo lipogenesis in liver and white adipose tissue. Because Mondo proteins mediate metabolic adaptations to changing glucose levels, a better understanding of cellular glucose sensing through Mondo proteins will likely uncover new therapeutic opportunities in the context of the imbalanced glucose homeostasis that accompanies metabolic diseases such as type 2 diabetes and cancer. Here, we provide an overview of structural homologies, transcriptional partners and the nutrient and hormonal mechanisms underlying Mondo proteins regulation. We next summarize their relative contribution to energy metabolism changes in physiological states and the evolutionary conservation of these pathways. Finally, we discuss their possible targeting in human pathologies.