Related Experiment Video
Updated: Sep 2, 2025
Dissecting Cell-Autonomous Function of Fragile X Mental Retardation Protein in an Auditory Circuit by In Ovo Electroporation
Published on: July 6, 2022
Sustained inhibition of NPY/AgRP neuronal activity by FGF1
Eunsang Hwang1, Jarrad M Scarlett2,3, Arian F Baquero4
1Department of Internal Medicine, Center for Hypothalamic Research, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA.
Abstract:
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.
Insights
Fibroblast growth factor 1 (FGF1) shows sustained antidiabetic effects in rodent models by inhibiting hypothalamic neurons. This FGF1-induced inhibition of NPY/AgRP neurons lasts for weeks, potentially explaining long-term glucose normalization in type 2 diabetes.
Area of Science:
- Neuroendocrinology
- Metabolic disease research
- Molecular signaling
Background:
- Rodent models of type 2 diabetes (T2D) exhibit hyperglycemia linked to increased NPY/AgRP neuron activity in the arcuate nucleus (ARC).
- Central administration of FGF1 in these models produces sustained normalization of blood glucose levels.
- The ARC is a critical brain region mediating FGF1's antidiabetic effects.
Purpose of the Study:
- To investigate whether FGF1 inhibits NPY/AgRP neurons.
- To determine if this inhibitory effect is long-lasting enough to explain sustained diabetes remission.
- To elucidate the mechanism underlying FGF1's action on NPY/AgRP neurons.
Main Methods:
- In vivo intracerebroventricular injection of FGF1 in rodent models.
- Ex vivo slice preparation of the ARC for direct neuronal application of FGF1.
- Electrophysiological recordings to assess NPY/AgRP neuron activity.
- Investigation of presynaptic GABAergic input.
Main Results:
- FGF1 administration inhibited NPY/AgRP neuron activity both in vivo and ex vivo.
- The mechanism involved enhanced input from presynaptic GABAergic neurons.
- The inhibitory effect of FGF1 on these neurons was sustained for at least 2 weeks post-administration.
Conclusions:
- FGF1 exerts a durable inhibitory effect on ARC NPY/AgRP neurons.
- This prolonged inhibition offers a potential explanation for the sustained antidiabetic action of FGF1.
- Further research is needed to confirm the contribution of NPY/AgRP neuron inhibition to FGF1's therapeutic effects in T2D models.
More Related Videos
Related Concept Videos
01:09GPCRs Regulate Adenylyl Cylase Activity
01:30Ligand-Gated Ion Channel Receptor: Gating Mechanism
01:12GPCR Desensitization