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

Overview

Authors: Yunfan Lin1,2,3,4,5,6, Kristin E Claflin1,2,3,6, Iltan Aklan4,5,6, Donald A Morgan1, Andrew I Sullivan1,2,3, Michael C Rudolph4,5, Kamal Rahmouni1,2,3,7,8, Matthew J Potthoff1,2,3,8,4,5,9
ORCID iDs: Michael C Rudolph
  1. Department of Neuroscience and Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
  2. Fraternal Order of Eagles Diabetes Research Center, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
  3. Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
  4. Harold Hamm Diabetes Center, University of Oklahoma Health Sciences, Oklahoma City, OK 73104, USA
  5. Department of Biochemistry and Physiology, University of Oklahoma Health Sciences, Oklahoma City, OK 73104, USA
  6. These authors contributed equally
  7. Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
  8. Iowa City VA Health Care System, Iowa City, IA 52242, USA
  9. Lead contact
Institutions: University of Iowa (United States); Fraternal Order of Eagles (United States); University of Oklahoma Health Sciences Center (United States); University of Oklahoma (United States); University of Iowa Health Care (United States); Iowa City VA Health Care System (United States); Iowa City VA Medical Center (United States)
Journal: Cell reports, volume 45, issue 4, article 117093
Dates: published online 31 March 2026; in print March 2026
Type: Research article · Language: English
License: CC BY-NC
Identifiers: DOI 10.1016/j.celrep.2026.117093 · PMID 41920739 · PMCID PMC13196181 · OpenAlex W7144289718
Open access: gold, a free copy (OpenAlex)
Status: code on request (how the code is found and verified)
Methods: Machine learning
Keywords: Body weight, Brown adipose tissue, Area postrema, Nucleus of the solitary tract, Fgf21, Betaklotho, Cp: Neuroscience, Cp: Metabolism
Topic: Fibroblast Growth Factor Research (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: NIDDK NIH HHS (R01 DK106104); University of Iowa; National Institute of Diabetes and Digestive and Kidney Diseases (R01DK106104); National Institutes of Health; NIA NIH HHS (R01 AG083950); U.S. Department of Veterans Affairs (I01 BX004249, I01BX004634, IK6 BX006040); BLRD VA (I01 BX004634); Pfizer (PF-05231023)
Citations: cited by 1 paper (Europe PMC); 87 references in the paper

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.

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Code

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Data reported in this paper will be shared by the lead contact upon request.

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Versions

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Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 8 authors, 8 keywords, 8 funders, 86 references.

Cite

This paper

Lin, Y., Claflin, K. E., Aklan, I., Morgan, D. A., Sullivan, A. I., Rudolph, M. C., Rahmouni, K., & Potthoff, M. J. (2026). Pharmacological administration of FGF21 reverses obesity through a parabrachial-projecting neuron population in the hindbrain. Cell reports, 45(4), 117093. https://doi.org/10.1016/j.celrep.2026.117093

BibTeX

@article{lin2026pharmacological,
author = {Lin, Yunfan and Claflin, Kristin E and Aklan, Iltan and Morgan, Donald A and Sullivan, Andrew I and Rudolph, Michael C and Rahmouni, Kamal and Potthoff, Matthew J},
title = {{Pharmacological administration of FGF21 reverses obesity through a parabrachial-projecting neuron population in the hindbrain}},
journal = {Cell reports},
year = {2026},
month = mar,
volume = {45},
number = {4},
pages = {117093},
publisher = {Cell Press},
issn = {2211-1247},
doi = {10.1016/j.celrep.2026.117093},
url = {https://doi.org/10.1016/j.celrep.2026.117093},
pmid = {41920739},
pmcid = {PMC13196181}
}

RIS

TY - JOUR
AU - Lin, Yunfan
AU - Claflin, Kristin E
AU - Aklan, Iltan
AU - Morgan, Donald A
AU - Sullivan, Andrew I
AU - Rudolph, Michael C
AU - Rahmouni, Kamal
AU - Potthoff, Matthew J
TI - Pharmacological administration of FGF21 reverses obesity through a parabrachial-projecting neuron population in the hindbrain
T2 - Cell reports
J2 - Cell Rep
PY - 2026
DA - 2026/03/31
VL - 45
IS - 4
SP - 117093
SN - 2211-1247
PB - Cell Press
DO - 10.1016/j.celrep.2026.117093
UR - https://doi.org/10.1016/j.celrep.2026.117093
LA - en
ER -

CSL-JSON

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