Sustained inhibition of NPY/AgRP neuronal activity by FGF1
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Sustained inhibition of NPY/AgRP neuronal activity by FGF1. / Hwang, Eunsang; Scarlett, Jarrad M.; Baquero, Arian F.; Bennett, Camdin M.; Dong, Yanbin; Chau, Dominic; Brown, Jenny M.; Mercer, Aaron J.; Meek, Thomas H.; Grove, Kevin L.; Phan, Bao Anh N.; Morton, Gregory J.; Williams, Kevin W.; Schwartz, Michael W.
In: JCI insight, Vol. 7, No. 17, e160891, 2022.Research output: Contribution to journal › Journal article › peer-review
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TY - JOUR
T1 - Sustained inhibition of NPY/AgRP neuronal activity by FGF1
AU - Hwang, Eunsang
AU - Scarlett, Jarrad M.
AU - Baquero, Arian F.
AU - Bennett, Camdin M.
AU - Dong, Yanbin
AU - Chau, Dominic
AU - Brown, Jenny M.
AU - Mercer, Aaron J.
AU - Meek, Thomas H.
AU - Grove, Kevin L.
AU - Phan, Bao Anh N.
AU - Morton, Gregory J.
AU - Williams, Kevin W.
AU - Schwartz, Michael W.
N1 - Publisher Copyright: © 2022, Hwang et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.
PY - 2022
Y1 - 2022
N2 - In rodent models of type 2 diabetes (T2D), central administration of FGF1 normalizes elevated blood glucose levels in a manner that is sustained for weeks or months. Increased activity of NPY/ AgRP neurons in the hypothalamic arcuate nucleus (ARC) is implicated in the pathogenesis of hyperglycemia in these animals, and the ARC is a key brain area for the antidiabetic action of FGF1. We therefore sought to determine whether FGF1 inhibits NPY/AgRP neurons and, if so, whether this inhibitory effect is sufficiently durable to offer a feasible explanation for sustained diabetes remission induced by central administration of FGF1. Here, we show that FGF1 inhibited ARC NPY/AgRP neuron activity, both after intracerebroventricular injection in vivo and when applied ex vivo in a slice preparation; we also showed that the underlying mechanism involved increased input from presynaptic GABAergic neurons. Following central administration, the inhibitory effect of FGF1 on NPY/AgRP neurons was also highly durable, lasting for at least 2 weeks. To our knowledge, no precedent for such a prolonged inhibitory effect exists. Future studies are warranted to determine whether NPY/AgRP neuron inhibition contributes to the sustained antidiabetic action elicited by intracerebroventricular FGF1 injection in rodent models of T2D.
AB - In rodent models of type 2 diabetes (T2D), central administration of FGF1 normalizes elevated blood glucose levels in a manner that is sustained for weeks or months. Increased activity of NPY/ AgRP neurons in the hypothalamic arcuate nucleus (ARC) is implicated in the pathogenesis of hyperglycemia in these animals, and the ARC is a key brain area for the antidiabetic action of FGF1. We therefore sought to determine whether FGF1 inhibits NPY/AgRP neurons and, if so, whether this inhibitory effect is sufficiently durable to offer a feasible explanation for sustained diabetes remission induced by central administration of FGF1. Here, we show that FGF1 inhibited ARC NPY/AgRP neuron activity, both after intracerebroventricular injection in vivo and when applied ex vivo in a slice preparation; we also showed that the underlying mechanism involved increased input from presynaptic GABAergic neurons. Following central administration, the inhibitory effect of FGF1 on NPY/AgRP neurons was also highly durable, lasting for at least 2 weeks. To our knowledge, no precedent for such a prolonged inhibitory effect exists. Future studies are warranted to determine whether NPY/AgRP neuron inhibition contributes to the sustained antidiabetic action elicited by intracerebroventricular FGF1 injection in rodent models of T2D.
U2 - 10.1172/jci.insight.160891
DO - 10.1172/jci.insight.160891
M3 - Journal article
C2 - 35917179
AN - SCOPUS:85137664478
VL - 7
JO - JCI Insight
JF - JCI Insight
SN - 2379-3708
IS - 17
M1 - e160891
ER -
ID: 320649792