Pharmacological administration of FGF21 reverses obesity through a parabrachial-projecting neuron population in the hindbrain

Yunfan Lin; Kristin E Claflin; Iltan Aklan; Donald A Morgan; Andrew I Sullivan; Michael C Rudolph; Kamal Rahmouni; Matthew J Potthoff

doi:10.1016/j.celrep.2026.117093

Back

Pharmacological administration of FGF21 reverses obesity through a parabrachial-projecting neuron population in the hindbrain

Journal article

Open access

Peer reviewed

Pharmacological administration of FGF21 reverses obesity through a parabrachial-projecting neuron population in the hindbrain

Yunfan Lin, Kristin E Claflin, Iltan Aklan, Donald A Morgan, Andrew I Sullivan, Michael C Rudolph, Kamal Rahmouni and Matthew J Potthoff

Cell reports (Cambridge), Vol.45(4), 117093

03/31/2026

DOI: 10.1016/j.celrep.2026.117093

PMID: 41920739

Files and links (1)

url

https://doi.org/10.1016/j.celrep.2026.117093View

Published (Version of record) Open Access

Abstract

The obesity epidemic is associated with significant healthcare and economic burdens. Pharmacological administration of the endocrine hormone fibroblast growth factor 21 (FGF21) increases energy expenditure and reverses obesity. However, the central targets and neural pathways for these metabolic benefits remain elusive. Here, we demonstrate that β-klotho (KLB)-expressing neurons in the hindbrain, specifically the nucleus of the solitary tract (NTS) and area postrema (AP), are both necessary and sufficient for FGF21's effect on energy expenditure and weight loss. These pharmacological benefits are mediated largely by NTS/AP KLB-expressing neurons that project to the parabrachial nucleus (PBN) and not the hypothalamus. Our results provide insights into the central mechanisms of pharmacological FGF21 action to modulate energy homeostasis.

area postrema

body weight

CP: neuroscience

brown adipose tissue

nucleus of the solitary tract

CP: metabolism

betaKlotho

FGF21

Details

Title: Subtitle: Pharmacological administration of FGF21 reverses obesity through a parabrachial-projecting neuron population in the hindbrain
Creators: Yunfan Lin - University of Iowa
Kristin E Claflin - University of Iowa
Iltan Aklan - University of Oklahoma Health Sciences Center
Donald A Morgan - University of Iowa
Andrew I Sullivan - University of Iowa
Michael C Rudolph - University of Oklahoma Health Sciences Center
Kamal Rahmouni - University of Iowa
Matthew J Potthoff - University of Iowa
Resource Type: Journal article
Publication Details: Cell reports (Cambridge), Vol.45(4), 117093
DOI: 10.1016/j.celrep.2026.117093
PMID: 41920739
NLM abbreviation: Cell Rep
ISSN: 2211-1247
eISSN: 2211-1247
Publisher: Cell Press
Grant note: National Institutes of Health (NIH): R01DK106104 Veterans Affairs Merit Review program: I01BX004634, K01DK133667 National Institutes of Health: R01 HL162773, R01 HL172944 US Department of Veterans Affairs: I01 BX004249, BX006040
We thank Dr. Birgitte Andersen (Novo Nordisk) for providing FGF21 protein. We thank Pfizer for providing PF-05231023. We thank Dr. Jon Resch (University of Iowa) for experimental input and expertise. This work is funded by the National Institutes of Health (NIH) R01DK106104 (M.J.P.), Veterans Affairs Merit Review program I01BX004634 (M.J.P.), and K01DK133667 (K.E.C.). K.R. is supported by the National Institutes of Health (R01 HL162773 and R01 HL172944) and the US Department of Veterans Affairs (I01 BX004249 and IK6 BX006040). The authors would like to acknowledge the use of the University of Iowa Central Microscopy Research Facility, the University of Iowa Metabolic Phenotyping Core, and the Genomics Division of the Iowa Institute of Human Genetics.
Language: English
Date published: 03/31/2026
Academic Unit: Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9985149086402771

Metrics

1 Record Views