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

Cell Reports 2026 Open access

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Authors: Yunfan Lin, Kristin E. Claflin, İltan Aklan, Donald A. Morgan, Andrew I. Sullivan, Michael C. Rudolph, Kamal Rahmouni, Matthew J. Potthoff
DOI: 10.1016/j.celrep.2026.117093
Cited by: 1
References: 85

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.

Fields of Study & Subjects

Fibroblast Growth Factor Research Nerve injury and regeneration Regulation of Appetite and Obesity

Publication details

Journal / source
Cell Reports
Publisher
Elsevier BV
Volume
45
Issue
4
Pages
117093–117093
Publication date
31 March 2026
Language
EN