Mechanisms by which carbohydrates regulate expression of genes for glycolytic and lipogenic enzymes

Abstract

Regulation of gene expression by nutrients is an important mechanism in the adaptation of mammals to their nutritional environment. This is especially true for enzymes involved in the storage of energy, such as the lipogenic and glycolytic enzymes in liver and adipose tissue. Transcription of the genes for lipogenic and glycolytic enzymes is stimulated by glucose in adipose tissue, liver, and pancreatic beta-cells. Several lines of evidence suggest that glucose must be metabolized to glucose-6-phosphate to stimulate gene transcription. In adipose tissue, insulin increases the expression of lipogenic enzymes indirectly by stimulating glucose uptake. In the liver, insulin also acts indirectly by stimulating the expression of glucokinase and, hence, by increasing glucose metabolism. Glucose response elements have been characterized for the L-pyruvate kinase and S14 genes. They have in common the presence of a sequence 5'-CACGTG-3', which binds a transcription factor called USF (upstream stimulatory factor). Another glucose response element, which uses a transcription factor named Sp1, has been characterized in the gene for the acetyl-coenzyme A carboxylase. The mechanisms linking glucose-6-phosphate to the glucose-responsive transcription complex are largely unknown.