Abstract
The expression of fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) is low in the adipose tissue of suckling rats and increases markedly at weaning to a high carbohydrate diet. We have studied in vitro the factors regulating this phenomenon. Inguinal adipose tissue pieces from 19-day-old suckling rats were cultured for 6 or 24 h in minimal essential medium. Insulin (100 nM) added in the presence of lactate and pyruvate did not stimulate the expression of FAS and ACC. Glucose (20 mM) alone resulted in a 5-7-fold increase of FAS and ACC mRNA. Insulin potentiated the effect of glucose. 3-O-Methylglucose, a glucose analog that is transported into the cell but not metabolized, had no effect on FAS and ACC mRNA accumulation. However, 2-deoxyglucose (1 mM), a glucose analog which is phosphorylated to 2-deoxyglucose 6-phosphate, stimulated the expression of FAS and ACC to the same extent as 20 mM glucose. Glucose 6-phosphate concentrations in adipose tissue pieces cultured in various conditions changed in parallel with the FAS and ACC mRNA levels. We conclude that glucose 6-phosphate could be the metabolite involved in the stimulation of lipogenic enzyme gene expression in response to glucose.
Highlights
Treatment of diabetic rats with insulin result in a coordinate increase of the activities of these enzymes [6,7,8,9]
Previous studies using cultured hepatocytes haveshown that carbohydrates increase the activities of hepatic lipogenic enzymes such as ATP-citrate lyase [24], malic enzyme (251, fatty acid synthase [3, 12] and acetyl-coA carboxylase [26]
Recent work demonstrates that glucose increases the mRNA concentrations and the transcription of glycolytic or lipogenic related proteins such as aldolase B [27], L-type pyruvate kinase [28], and spot S14 [29] whereas it decreases that of PEPCK [30]
Summary
Treatment of diabetic rats with insulin result in a coordinate increase of the activities of these enzymes [6,7,8,9]. FAS and ACC activities and mRNA are low in of suckling rats and increases markedly at weaning to the adipose tissue of suckling rats andincrease after weaning a high carbohydratediet. We have studied in vitro the to a high carbohydrate low fat diet [13, 14] In the rat, it is factors regulating this phenomenon. Glucose 6phosphate concentrationsin adipose tissue pieces culcarbohydrate diet, to thelaboratory chow, a high carbohydrate low fat diet [15]. A single carbohydrate meal is able to induce the expression of these enzymes in suckling rats [14] These in vivo studies suggested that glucose and/or insulin could play a major role in the regulation of these enzymes in adipose tissue.
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