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.
Foufelle
F
F
Centre de Recherches sur l'Endocrinologie Moléculaire et le Développement, Centre National de la Recherche Scientifique, Meudon-Bellevue, France.
Gouhot
B
B
Pégorier
J P
JP
Perdereau
D
D
Girard
J
J
Ferré
P
P
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