AUTHOR=Benhamed Fadila , Filhoulaud Gaelle , Caron Sandrine , Lefebvre Philippe , Staels Bart , Postic Catherine TITLE=O-GlcNAcylation Links ChREBP and FXR to Glucose-Sensing JOURNAL=Frontiers in Endocrinology VOLUME=5 YEAR=2015 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2014.00230 DOI=10.3389/fendo.2014.00230 ISSN=1664-2392 ABSTRACT=

Accumulating evidence suggests that O-GlcNAc transferase, an enzyme responsible for O-GlcNAc post-translational modification acts as a nutrient sensor that links glucose and the hexosamine biosynthetic pathway to the regulation of transcriptional factors involved in energy homeostasis. In liver, glucose signaling is mediated by carbohydrate response element-binding protein (ChREBP), which stimulates glycolytic and lipogenic gene expression through its binding on a specific ChoRE DNA sequence. Modulation of ChREBP by O-GlcNAcylation increases its DNA binding affinity and its activity. ChREBP transcriptional activity also depends on the presence of several other co-factors and transcriptional factors. Among them, the nuclear Farnesoid X Receptor (FXR), a key transcription factor of bile acid metabolism involved in the gut–liver axis homeostasis was recently shown to directly interact with ChREBP, acting as a repressor on the ChoRE of glycolytic genes. Interestingly, similarly to ChREBP, FXR is O-GlcNAcylated in response to glucose. This review discusses the importance of ChREBP and FXR modifications through O-GlcNAcylation in liver and how glucose can modify their mutual affinity and transcriptional activity.