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

Autor: Torz L; In Vitro Obeisty Research, Novo Nordisk, 2760 Måløv, Denmark.; Section for Experimental Animal Models, Department of Veterinary and Animal Sciences, University of Copenhagen, 1870 Frederiksberg, Denmark., Niss K; Bioinformatics & Data Mining, Novo Nordisk, 2760 Måløv, Denmark., Lundh S; Pathology & Imaging, Novo Nordisk, 2760 Måløv, Denmark., Rekling JC; Department of Neuroscience, University of Copenhagen, 2200 Copenhagen, Denmark., Quintana CD; Cell Therapy R&D, Novo Nordisk, 2760 Måløv, Denmark., Frazier SED; Cell Therapy R&D, Novo Nordisk, 2760 Måløv, Denmark., Mercer AJ; Target Discovery Platforms, Novo Nordisk, Seattle, WA 98109, USA., Cornea A; Target Discovery Platforms, Novo Nordisk, Seattle, WA 98109, USA., Bertelsen CV; Cell Therapy R&D, Novo Nordisk, 2760 Måløv, Denmark., Gerstenberg MK; GOLD In Vivo Pharmacology DK I, Novo Nordisk, 2760 Måløv, Denmark., Hansen AMK; In Vitro Obeisty Research, Novo Nordisk, 2760 Måløv, Denmark., Guldbrandt M; In Vitro Obeisty Research, Novo Nordisk, 2760 Måløv, Denmark., Lykkesfeldt J; Section for Experimental Animal Models, Department of Veterinary and Animal Sciences, University of Copenhagen, 1870 Frederiksberg, Denmark., John LM; GOLD In Vivo Pharmacology DK I, Novo Nordisk, 2760 Måløv, Denmark., Villaescusa JC; Cell Therapy R&D, Novo Nordisk, 2760 Måløv, Denmark., Petersen N; In Vitro Obeisty Research, Novo Nordisk, 2760 Måløv, Denmark.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2022 Mar 17; Vol. 23 (6). Date of Electronic Publication: 2022 Mar 17.
DOI: 10.3390/ijms23063260
Abstrakt: 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.
Databáze: MEDLINE
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