ChREBP is a protein in the liver that helps in the metabolism of glucose and the stores fat in the body. ChREBP acts as a transcript factor in sorting out the gene activated by glucose appearance of numerous enzymes in the liver, that are accountable for conversion of surplus carbohydrate to fats. ChREBP is translocate into the nucleus with the help of high levels of glucose, and later on-regulates transcriptional activity.
When serum glucose increase in level, the isoforms of glucose transporter kinase (hexokinase IV) and GLUT2, appear in the hepatocyte and facilitate equilibration and rapid uptake of intracellular glucose levels. This fluctuation of glucose endorses the hexose monophosphate path to form xylulose-5-phosphate, which consequentially activate protein phosphatase 2A to dephosphorylate ChREBP and encourage DNA binding and nuclear localization. In addition, continuous exposure of hepatocytes to increased level of insulin and glucose results in amplified quantities of these main enzymes through improved translation and transcription.
Polyunsaturated fatty acids are observed to hold back ChREBP activity in hepatocytes by elevating the decay rate of ChREBP mRNA. The specific molecular mechanisms by which these translational and transcriptional regulatory processes occur to inhibit ChREBP activity wait for more investigation.
Overexpression of max-like protein X (Mlx) led to the exposition of the ChREBP functions. Since high levels of glucose induce glycosylation of proteins in the cells, the consequence of O-linked GlcNAc alteration on ChREBP functions was studied. Treatment with an O-GlcNAcase inhibitor (PUGNAc), which elevated the O-linked GlcNAc alteration of proteins in the cells, resulted to an increase in the glucose reaction of ChREBP. On the contrary, DON treatment also lowers O-GlcNAcylation by slowing down the hexosamine biosynthetic conduit; it blocks the glucose reaction of ChREBP.
Mice appear to be very intolerant of diets that contain considerable sucrose or fructose, rapidly exhibiting hypothermia, losing weight and declining within days. This is due low levels of enzymes that are necessary for fructose in the process glycolysis. In general, the loss of hepatic ChREBP leads to impaired glucose flux.