Glucose stimulation of lipogenic enzyme gene expression in cultured white adipose tissue. A role for glucose 6-phosphate.
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.
Centre de Recherches sur l'Endocrinologie Moléculaire et le Développement, Centre National de la Recherche Scientifique, Meudon-Bellevue, France.
F
F
Foufelle
B
B
Gouhot
J P
JP
Pégorier
D
D
Perdereau
J
J
Girard
P
P
Ferré
D019325:3-O-Methylglucose; D000103:Acetyl-CoA Carboxylase / Q000235:genetics*; D000273:Adipose Tissue / Q000187:drug effects / Q000201:enzymology*; D000818:Animals; D000833:Animals, Suckling; D002478:Cells, Cultured; D064429:Fatty Acid Synthases / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology*; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008757:Methylglucosides / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014886:Weaning
D005958:Glucosephosphates; D007328:Insulin; D008757:Methylglucosides; D012333:RNA, Messenger; D019325:3-O-Methylglucose; D019298:Glucose-6-Phosphate; D064429:Fatty Acid Synthases; D000103:Acetyl-CoA Carboxylase; D005947:Glucose