Evidence map›Paper›PMID 41679434›Full record

ArticleMolecular metabolism2026

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

Daniel Shookster, Shea O'Connell, Patel Darshan, Taylor Landry, Wyatt Bunner, Zhiying Jiang, Qingchun Tong, Hu Huang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Daniel ShooksterEast Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC, USA; Department of Kinesiology, East Carolina University, Greenville, NC, USA; Human Performance Laboratory, College of Human Performance and Health, East Carolina University, Greenville, NC, USA.
Shea O'ConnellEast Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC, USA; Department of Kinesiology, East Carolina University, Greenville, NC, USA; Human Performance Laboratory, College of Human Performance and Health, East Carolina University, Greenville, NC, USA.
Patel DarshanEast Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC, USA; Department of Kinesiology, East Carolina University, Greenville, NC, USA; Human Performance Laboratory, College of Human Performance and Health, East Carolina University, Greenville, NC, USA.
Taylor LandryEast Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC, USA; Department of Kinesiology, East Carolina University, Greenville, NC, USA; Human Performance Laboratory, College of Human Performance and Health, East Carolina University, Greenville, NC, USA.
Wyatt BunnerEast Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC, USA; Department of Kinesiology, East Carolina University, Greenville, NC, USA; Human Performance Laboratory, College of Human Performance and Health, East Carolina University, Greenville, NC, USA.
Zhiying JiangBrown Foundation Institute of Molecular Medicine of McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
Qingchun TongBrown Foundation Institute of Molecular Medicine of McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
Hu HuangEast Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC, USA; Department of Kinesiology, East Carolina University, Greenville, NC, USA; Human Performance Laboratory, College of Human Performance and Health, East Carolina University, Greenville, NC, USA; Department of Physiology, East Carolina University, Greenville, NC, USA. Electronic address: huangh@ecu.edu.

Funding

FGFR1 Signaling in AgRP Neurons for Regulating MetabolismR15DK139539 · NIDDK · EAST CAROLINA UNIVERSITY · PI HUANG, HU · 2025 to 2025
$453k
The central role of alpha-klotho in regulation of metabolismR15DK121215 · NIDDK · EAST CAROLINA UNIVERSITY · PI HUANG, HU · 2019 to 2019
$443k
NIDDK NIH HHS R15 DK121215NIDDK NIH HHS R15 DK139539
6 · The paper itself

Abstract

backgroundThe 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.

methodsTo 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.

resultsDeletion 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 neurons and abolished the suppressive effect of α-Klotho on their activity. At the molecular level, FGFR1 knockdown decreased phosphorylation of the transcription factor FOXO1 and elevated AgRP mRNA expression.

conclusionsOur results define a crucial FGFR1 signaling axis in AgRP neurons that coordinately regulates their electrical activity and peptide expression, thereby establishing FGFR1 as an essential regulator of energy homeostasis.

Indexed as

Agouti-Related ProteinEnergy MetabolismNeuronsReceptor, Fibroblast Growth Factor, Type 1AnimalsDiet, High-FatForkhead Box Protein O1HomeostasisKlotho ProteinsMaleMiceMice, Inbred C57BLMice, KnockoutObesitySignal TransductionAgouti-Related ProteinAgrp protein, mouseFgfr1 protein, mouseForkhead Box Protein O1Klotho ProteinsReceptor, Fibroblast Growth Factor, Type 1AgRP neuronEnergy homeostasisFGFR1High fat diet

Identifiers

PMID41679434
PMCPMC12936525

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.