Carbohydrate-responsive element-binding protein (ChREBP)

Carbohydrate-responsive element-binding protein (ChREBP) is a nutrient-sensitive transcription factor mainly expressed in the liver, adipose tissue, and pancreatic β-cells. It plays a central role in the genomic response to carbohydrate intake by activating genes needed for glycolysis and fatty acid synthesis in response to increased glucose levels. ChREBP is part of the Mondo family (bHLH-Zip structure), acting downstream of glucose signaling independently of insulin. It has two main isoforms (ChREBPα and ChREBPβ), arising from alternative promoters in the Mlxipl gene; the β-isoform is constitutively nuclear and transcriptionally hyperactive. Under high glucose, ChREBP translocates to the nucleus and binds carbohydrate-responsive elements on target genes, driving metabolic and sometimes inflammatory responses. Dysregulation of ChREBP activity has been linked to metabolic diseases, including diabetes and fatty liver, and has become a focus for therapeutic modulation, with experimental small molecules under early investigation.

Other names

MLX-interacting protein-like (MLXIPL)MondoBWBSCR14

Small molecules that stabilize ChREBP/14-3-3 interaction can sequester ChREBP in the cytoplasm, thereby inhibiting its role in glucose-induced gene expression and β-cell apoptosis under glucolipotoxic conditions.