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

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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.

OriginalsprogEngelsk
Artikelnummer3260
TidsskriftInternational Journal of Molecular Sciences
Vol/bind23
Udgave nummer6
Antal sider15
ISSN1661-6596
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
Funding: L.T. and J.L. were partly funded by the LifePharm Centre for In Vivo Pharmacology at University of Copenhagen (grant number: 1001109652).

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

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