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 (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.

Authors Torz L, Niss K, Lundh S, Rekling JC, Quintana CD, Frazier SED, Mercer AJ, Cornea A, Bertelsen CV, Gerstenberg MK, Hansen AMK, Guldbrandt M, Lykkesfeldt J, John LM, Villaescusa JC, Petersen N
Journal International journal of molecular sciences
Publication Date 2022 Mar 17;23(6)
PubMed 35328681
PubMed Central PMC8948797
DOI 10.3390/ijms23063260

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