Vanadate elevates lipogenicity of starved rat adipose tissue: mechanism of action.
We have established an experimental system in rats in which the lipogenic capacity of adipose tissue was decreased in vivo by prolonged fasting, and restored in vitro by glucose together with insulin or vanadate. Incubation of fasted adipose explants for 5 h at 37 C with 2 mM glucose alone did not elevate lipogenic capacity. However, glucose with insulin (17 nM) or vanadate (100 microM), led, respectively, to 2.2- and 8- to 10-fold elevation. Actinomycin D (50 microM) completely blocked this increase, while low concentrations (ED50 = 4.0 +/- 0.4 microM) of vanadate potentiated it. Neither insulin nor vanadate elevated fasted adipose explants' lipogenic capacity in the absence of glucose, or in the presence of the nonmetabolizable glucose analog 3-O-methylglucose. Upon replacing glucose with 2-deoxyglucose (1 mM), a glucose analog that undergoes phosphorylation to 2-deoxyglucose-6-phosphate with no further metabolism, vanadate was nearly as potent as with glucose in elevating lipogenic capacity. Vanadate was superior to insulin in increasing glucose-6-phosphate level in fasted-adipose explants. Adipose glucose-6-phosphatase activity was inhibited by vanadate (IC50 = 7.0 +/- 0.4 microM). We have concluded that glucose-6-phosphate is the key metabolite of glucose involved in the transcriptionally regulated elevation of lipogenic capacity of fasted adipose explants. Vanadate has a more profound effect than insulin, as it elevates glucose-6-phosphate to higher levels and the subsequent increase in lipogenic capacity is four to five times greater than that induced by insulin. The mechanism involved is the combined action of vanadate in enhancing glucose entry and in inhibiting dephosphorylation of endogenously formed glucose-6-phosphate. The latter effect is not exerted by insulin.
Sekar
N
N
Department of Biological Chemistry, The Weizmann Institute of Science Rehovot, Israel.
Qian
S
S
Shechter
Y
Y
D019325:3-O-Methylglucose / Q000378:metabolism / Q000494:pharmacology; D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D003847:Deoxyglucose / Q000378:metabolism / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005215:Fasting; D005947:Glucose / Q000494:pharmacology; D005952:Glucose-6-Phosphatase / Q000037:antagonists & inhibitors; D019298:Glucose-6-Phosphate / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D008055:Lipids / Q000096:biosynthesis*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014638:Vanadates / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D007328:Insulin; D008055:Lipids; D019325:3-O-Methylglucose; D014638:Vanadates; D019298:Glucose-6-Phosphate; D003847:Deoxyglucose; D005952:Glucose-6-Phosphatase; D005947:Glucose