Orthovanadate decreases leptin secretion from isolated mouse fat pads.
When isolated mouse fat pads were incubated with orthovanadate (vanadate) or insulin for up to 4 h, the leptin secretion into the medium was decreased by vanadate and increased by insulin. Propranolol, a nonspecific antagonist of beta-adrenergic receptors, bupranorol, a specific antagonist of beta3-adrenergic receptor, and H-89, an inhibitor of cAMP-dependent protein kinase (PKA) all inhibited the decrease by vanadate to various extents. In contrast, no inhibition was observed with specific antagonists of beta1- and beta2-adrenergic receptors or with inhibitors of protein kinase C and Ca/calmodulin kinase. Short-term incubation of the fat pads with vanadate showed a transient increase in the cellular cAMP content; this increase was inhibited by propranolol and bupranolol. Vanadate had no effect on the incorporation of [3H]-leucine into proteins of the fat pads with a 4-h incubation, although insulin stimulated the incorporation. The decreasing effect of vanadate on the leptin secretion seems to be independent of the regulation of protein synthesis. These results suggest that vanadate decreases the leptin secretion through mechanisms involving the increase in cellular cAMP content via beta3-adrenergic receptor, probably leading to the activation of PKA.
Suenaga
T
T
Department of Biochemistry, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Hiroshima, Japan.
Hirano
K
K
Yoshida
A
A
Motoyashiki
T
T
Morita
T
T
Ueki
H
H
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D003864:Depression, Chemical; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D020738:Leptin / Q000378:metabolism*; D007930:Leucine / Q000378:metabolism; D008297:Male; D051379:Mice; D022702:Receptors, Adrenergic, beta-3 / Q000187:drug effects / Q000378:metabolism; D054411:Receptors, Leptin; D014638:Vanadates / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D020738:Leptin; D022702:Receptors, Adrenergic, beta-3; D054411:Receptors, Leptin; C515447:leptin receptor, mouse; D014638:Vanadates; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D007930:Leucine