Advertisement

Sustained inhibition of NPY/AgRP neuronal activity by FGF1

Eunsang Hwang,¹ Jarrad M. Scarlett,² Arian F. Baquero,³ Camdin Bennett,³ Yanbin Dong,¹ Dominic Chau,¹ Jenny M. Brown,⁴ Aaron J. Mercer,³ Thomas H. Meek,³ Kevin L. Grove,³ Bao Anh N. Phan,⁴ Gregory J. Morton,⁴ Kevin W. Williams,¹ and Michael W. Schwartz⁴

Published August 2, 2022 - More info

In rodent models of type 2 diabetes (T2D), central administration of fibroblast growth factor 1 (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 inhibits ARC NPY/AgRP neuron activity, both after icv injection in vivo and when applied ex vivo in a slice preparation, and that the underlying mechanism involves increased input from presynaptic GABAergic neurons. Following central administration, the inhibitory effect of FGF1 on NPY/AgRP neurons is also highly durable, lasting for at least two 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 icv FGF1 injection in rodent models of T2D.

Advertisement

Advertisement