Figure 6: High-fat feeding alters leptin’s action on sIPSCs.

(a,b) Representative sample traces showing sIPSCs recorded from POMC neurons in animals fed HFD for 3 weeks. In contrast to the control group, leptin significantly increased sIPSC frequency at 10 mM glucose (a). Leptin reduced sIPSC frequency, suggesting that the AMPK activator completely reverses leptin’s action on sIPSCs. HP=−70 mV. (c,d). Sample recording traces showing sIPSCs recorded from POMC neurons in animals on HFD in the presence of the MC3/4R antagonist alone or the MC3/4R and mGluR antagonists. Leptin had an inhibitory effect on sIPSCs under these conditions. HP=−70 mV. Scale bar, 100 pA, 10 s. (e) Summary plot showing leptin’s net effect on sIPSCs recorded from POMC neurons at 10 mM glucose in animals fed NCD and HFD. Leptin had opposing effects on sIPSCs at 10 mM glucose in animals fed NCD and HFD (n=14 neurons). Leptin’s stimulatory effect was completely inhibited by the AMPK activator and MC3/4R antagonist (A769662, n=7 neurons; SHU9119, n=8 neurons; MCPG+SHU9119, n=8 neurons). NCD, normal chow diet; HFD, high-fat diet. (f) Sample recording traces (left) and summary plot (right) of sIPSCs recorded from POMC neurons in animals microinjected with the PI3K activator or the activator plus the MC3/4R and mGluR antagonists. Injection of the PI3K activator strongly increased sIPSC frequency, which was completely blocked by the MC3/4R and mGluR antagonists (n=24 and 16 neurons, respectively). Scale bar, 100 pA, 10 s. *P<0.05, **P<0.01, ***P<0.001 versus control (paired t-test). All data are shown as mean±s.e.m.