growth/size/body
• treatment with 25 ug/g of leptin results in significant decrease in body weight in Lepob homozygotes compared to wild-type littermates
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nervous system
• Lepob homozygotes have a lower total number of synapses onto perikarya of Arcuate nucleus Pomc neurons compared to wild-type littermates; in wild-type, exciitory synapses on Pomc neurons are more numerous than inhibitory synapses, whereas in Lepob homozygotes, inhibitory synapses on Pomc neurons are more numerous
• altered synaptic profile is consistent with increased inhibitory tone on Pomc neurons in Lepob homozygotes
• 6 hours after leptin injection, an increase in total number of synapses on Pomc perikarya is detected, with an increase in excitatory inputs to Pomc cells; after 2 days of leptin treatment, synapse number onto Pomc neurons is doubled with a 300% increase in excitatory synapse number in Lepob homozygotes
• similar changes in synaptic profile are observed after 12 days of treatment
• after 4 days of twice-daily injections of 10 ug of ghrelin, number of excitatory inputs on Pomc neurons is decreased and number of inhibitory inputs is increased compared to saline-treated Lep mice (opposite to effect of leptin treatment)
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• in Lepob homozygotes, there are 2-fold more inhibitory postsynaptic currents (IPSCs) as excitatory postsynaptic currents (EPSCs) onto Pomc neurons in the Arcuate nucleus in hypothalamic slices compared to wild-type mice
• 2 days of leptin treatment decreased frequency of spontaneous IPSCs onto Pomc neurons in Lepob homozygotes
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behavior/neurological
• treatment with 25 ug/g of leptin results in significant decrease in food intake after 2 and 12 days treatment
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• after 4 days of twice-daily injections of 10 ug of ghrelin, an increase in food intake is observed
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