Selective deletion of FGFR1 in AgRP neurons impairs energy homeostasis under high-fat diet in mice.

ABSTRACT:

Background

The global obesity crisis and the limited success of current treatments underscore the need to identify novel regulatory pathways. While central administration of α-Klotho exerts anti-obesity effects in rodents through AgRP neurons, the intracellular signaling mechanisms that mediate this process remain undefined.

Methods

To define the role of FGFR1 within the α-Klotho signaling pathway in AgRP neurons, we performed a targeted deletion of the receptor in adult mice using an AAV-mediated CRISPR/Cas9 system alongside transgenic models.

Results

Deletion of FGFR1 in AgRP neurons disrupted energy homeostasis, promoting weight gain induced by a high-fat diet. Electrophysiological recordings revealed that FGFR1 loss increased the intrinsic firing rate of AgRP neur

SUBMITTER: Shookster D 

PROVIDER: S-EPMC12936525 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature