What question did this study set out to answer?

This research aims to identify the neural pathways through which FGF21 affects energy expenditure and weight loss.

April 4, 2026Open Access

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

Key Points

This research aims to identify the neural pathways through which FGF21 affects energy expenditure and weight loss.
Administered FGF21 pharmacologically to assess its effects on obesity.
Identified and targeted β-klotho-expressing neurons in the hindbrain regions like NTS and AP.
Analyzed the neural connections between these neurons and the parabrachial nucleus.
FGF21 administration significantly increased energy expenditure and reduced body weight.
The effects were primarily mediated by KLB-expressing neurons in the NTS and AP, which project to the PBN.
The hypothalamus was not involved in mediating these effects.

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.

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