Sirtuin 1 Regulates Synapsin 1 in POMC-Producing N43-5 Neurons via FOXO1

Abstract The nutrient-sensor protein Sirtuin 1 (Sirt1; silent mating type information regulation 2 homolog 1) has been shown to have significant and opposing effects on insulin resistance, leptin body weight in the periphery brain. In hypothalamic arcuate nucleus (ARC) of brain, Sirt1 increases obese state acts promote gain as well resistance by increasing orexigenic neuropeptides Agouti-related (AgRP) neuropeptide Y (NPY), a distinct set ARC neurons, decreasing POMC thus its anorexigenic derivative alpha-melanocyte stimulating hormone (alpha-MSH) (1). Sirt1’s actions these are mediated at least part deacetylation transcription factor forkhead box O1 (FOXO1). Another mechanism which regulates appears be through mediating changes synapses neuropeptide-producing neurons. For example, previous study demonstrated that inhibition with specific inhibitor, Ex-527, decreased AgRP-NPY inhibitory synaptic input suggests obesity-induced increase would neurons promoting (2). present investigated how specifically POMC-producing N43-5 Results reveal Ex-527 significantly increased presynaptic marker Synapsin (Syn1) Furthermore, we whether target, FOXO1, mediates changes. FOXO1 overexpression Syn1 transfection mutant Syn1. Overall, our results suggest does so manner differs from neuronal synapses. Future work will elucidate mechanisms consequences neuron under different nutritional conditions vitro vivo. (1) Cyr, N. E., Steger, J. S., Toorie, A. M., Yang, Z., Stuart, R., Nillni, E. (2014). Central Regulates Body Weight Energy Expenditure Along With POMC-Derived Peptide α-MSH Processing Enzyme CPE Production Diet-Induced Obese Male Rats, Endocrinology, 155(7), 2423–2435. (2) Dietrich, M. O., Antunes, C., Geliang, G., Liu, Borok, Nie, Y., . Horvath, T. L. (2010). Agrp mediate action melanocortin system energy balance: Roles for firing plasticity. Journal Neuroscience, 30(35), 11815–11825.