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- W4377029346 abstract "<b>Abstract ID 26676</b> <b>Poster Board 273</b> Maternal obesity influences susceptibility of offspring to Obesity and Type-II diabetes (T2D). Animal studies of maternal overnutrition have demonstrated alterations in the circuits driving metabolic homeostasis. More specifically, hypothalamic circuits that regulate energy expenditure and food intake. Previously, we reported on a subset of neurons (Agouti-related Peptide-AgRP/Neuropeptide Y – NPY), that are essential to metabolic homeostasis in the mediobasal hypothalamic arcuate nucleus (ARC). These neurons are uniquely enmeshed by perineuronal net (PNN)- like structures, which coincides with the critical-period (before postnatal day 28 or P28) closure in this area. To study the consequence and impact of maternal overnutrition on AgRP neurons, we subjected nursing dams to either high fat diet (maternal High Fat diet- mHFD) or normal chow diet (maternal Normal Chow diet- mNCD) during their lactation period. We found ARC PNNs formed earlier (premature) and a leptin surge observed sooner and at higher levels in pups subjected to mHFD compared to mNCD. Through indirect calorimetry studies we showed that mHFD exposed mice reduced their food intake but no change in their energy expenditure was observed. These results suggest that mHFD may influence the inhibitory synaptic transmission of AgRP/NPY neurons. In slice electrophysiology studies probing the synaptic transmission and neuronal excitability of AgRP/NPY neurons, we found that AgRP/NPY neurons in mHFD mice at P21 displayed a lower firing rate, and higher amplitude of spontaneous and miniature inhibitory postsynaptic currents (sIPSC and mIPSC), but no effect on spontaneous and miniature excitatory postsynaptic currents (sEPSC and mEPSC). Overall, we infer that maternal overnutrition altered the activity of AgRP neurons, thereby modifying hypothalamic arcuate circuits, leading to metabolic dysfunction. Future work regarding the impact of early maturation of PNNs as a result of maternal overnutrition during postnatal development are being explored. This project is funded by DOD grant." @default.
- W4377029346 created "2023-05-19" @default.
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- W4377029346 date "2023-05-18" @default.
- W4377029346 modified "2023-09-29" @default.
- W4377029346 title "Impact of Maternal Overnutrition in Central Nervous System Circuits that Regulate Feeding" @default.
- W4377029346 doi "https://doi.org/10.1124/jpet.122.266760" @default.
- W4377029346 hasPublicationYear "2023" @default.
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