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NPFF Decreases Activity of Human Arcuate NPY Neurons: A Study in Embryonic-Stem-Cell-Derived Model

Restoring the control of food intake is the key to obesity management and prevention. The arcuate nucleus (ARC) of the hypothalamus is extensively being studied as a potential anti-obesity target. Animal studies showed that neuropeptide FF (NPFF) reduces food intake by its action in neuropeptide Y (...

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Detalles Bibliográficos
Autores principales: Torz, Lola, Niss, Kristoffer, Lundh, Sofia, Rekling, Jens C., Quintana, Carlos Damian, Frazier, Signe Emilie Dannulat, Mercer, Aaron J., Cornea, Anda, Bertelsen, Charlotte Vinther, Gerstenberg, Marina Kjærgaard, Hansen, Ann Maria Kruse, Guldbrandt, Mette, Lykkesfeldt, Jens, John, Linu Mary, Villaescusa, J. Carlos, Petersen, Natalia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8948797/
https://www.ncbi.nlm.nih.gov/pubmed/35328681
http://dx.doi.org/10.3390/ijms23063260
Descripción
Sumario:Restoring the control of food intake is the key to obesity management and prevention. The arcuate nucleus (ARC) of the hypothalamus is extensively being studied as a potential anti-obesity target. Animal studies showed that neuropeptide FF (NPFF) reduces food intake by its action in neuropeptide Y (NPY) neurons of the hypothalamic ARC, but the detailed mode of action observed in human neurons is missing, due to the lack of a human-neuron-based model for pharmacology testing. Here, we validated and utilized a human-neural-stem-cell-based (hNSC) model of ARC to test the effects of NPFF on cellular pathways and neuronal activity. We found that in the human neurons, decreased cAMP levels by NPFF resulted in a reduced rate of cytoplasmic calcium oscillations, indicating an inhibition of ARC NPY neurons. This suggests the therapeutic potential of NPFFR2 in obesity. In addition, we demonstrate the use of human-stem-cell-derived neurons in pharmacological applications and the potential of this model to address functional aspects of human hypothalamic neurons.