In vivo and in vitro experiments strongly support the view that marked increases in the levels of mRNA and in the activities of lipogenic enzymes that occur in liver and white adipose tissue of the rat after weaning to a high‐carbohydrate diet are dependent on an increase in plasma glucose and insulin concentrations. An increased glucose metabolism is necessary for the expression of insulin effects on fatty acid synthase (FAS) and acetyl‐CoA carboxylase (ACC) mRNA accumulation in white adipose tissue, as insulin is ineffective in vitro in the absence of glucose. It is suggested that intracellular glucose‐6‐phosphate could play an important role in the effect of insulin on lipogenic enzyme gene expression in white adipose tissue. Other hormones and substrates could also play a role in the surge of lipogenesis after weaning. The fall in plasma glucagon after weaning to a high‐carbohydrate diet could reinforce the insulin‐induced accumulation of FAS and ACC mRNA, as this hormone inhibits the accumulation of lipogenic enzyme mRNA in liver and white adipose tissue. The decrease in the dietary supply of fat after weaning to a high‐carbohydrate diet could also potentiate the accumulation of FAS and ACC mRNA in liver because long‐chain polyunsaturated fatty acids are potent inhibitors of the expression of the genes encoding liver lipogenic enzymes. A direct effect of fatty acids on a cis‐acting element of the lipogenic enzyme genes could be involved, as the regulatory region of FAS gene contains a polyunsaturated fatty acid response element that shares some similarity with the peroxisome proliferator‐activated receptor recently described.— Girard, J., Perdereau, D., Foufelle, F., Prip‐Buus, C., Ferré, P. Regulation of lipogenic enzyme gene expression by nutrient and hormones.FASEB J.8: 36‐42; 1994.