Stimulation of phosphoenolpyruvate carboxykinase gene expression by fatty acids

We used the 3T3-F442A adipocytes and the FAO hepatoma cells to analyze the effect of oleate on phosphoenolpyruvate carboxykinase (PEPCK) gene expression. In serum-deprived, glucose-free medium, 1 mM oleate, bound to albumin in a 6:1 ratio, specifically stimulated PEPCK mRNA. In 3T3-F442A adipocytes, the maximum 5-fold increase occurred in 4 hours then rapidly declined to reach the basal level 20 hours later. This increase was cycloheximide-independent and actinomycin D-dependent, suggesting a direct, transcriptional effect of oleate. FAO cells also responded to oleate with a transient induction of PEPCK mRNA, although the extent of stimulation was lower. Thus, the PEPCK gene provides a useful molecular tool for studying the mechanisms by which fatty acids stimulate gene expression.