出版社：American Society for Biochemistry and Molecular Biology
摘要：An anti-leptin receptor polyclonal antibody (receptor antibody), as well as leptin, stimulated the release of free fatty acids from isolated mouse fat pads in a time-dependent manner. Following a 90-min incubation, maximal lipolysis was observed at 6 μg/ml receptor antibody and 0.1 nM leptin. The receptor antibody did not show any additive effect to the stimulation of lipolysis induced by leptin, suggesting that they exert their actions through a similar mechanism involving the leptin receptor. N -[2-( p -bromocinnamylamino) ethyl]-5-isoquinolinesulfonamide (H-89), quin 2-AM, N -(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide (W-7), and neomycin sulfate (neomycin) all potently inhibited the stimulation of lipolysis by the receptor antibody and leptin. Short-term incubation of the fat pads with the receptor antibody or leptin showed a transient increase in the cellular content of cAMP and myo -inositol 1,4,5-trisphosphate (IP3) in similar concentrations to the free fatty acid release. Quin 2-AM and W-7 also inhibited the increase in cAMP content, suggesting that a Ca2+/calmodulin-dependent process may be involved in a part of the mechanism in which the receptor antibody and leptin exert their effects. The increase in cellular IP3 content via phosphoinositide-specific phospholipase C (PLC) sensitive to neomycin appears to be a primary step to initiate intracellular events. Both the receptor antibody and leptin may stimulate the lipolysis through mechanisms involving a transient increase in the cellular IP3 content followed by cAMP production, which leads to the activation of cAMP-dependent protein kinase. —Kawaji, N., A. Yoshida, T. Motoyashiki, T. Morita, and H. Ueki. Anti-leptin receptor antibody mimics the stimulation of lipolysis induced by leptin in isolated mouse fat pads. J. Lipid Res. 2001. 42: 1671–1677.
