Orthovanadate Decreases Leptin Secretion from Isolated Mouse Fat Pads.

SUENAGA Tomohiro, HIRANO Ken, YOSHIDA Aya, MOTOYASHIKI Toshio, MORITA Tetsuo, UEKI Hiroshi

doi:10.1248/bpb.24.327

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 β-adrenergic receptors, bupranorol, a specific antagonist of β₃-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 β₁- and β₂-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 β₃-adrenergic receptor, probably leading to the activation of PKA.

Orthovanadate Decreases Leptin Secretion from Isolated Mouse Fat Pads.

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