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Updated: Jan 10, 2026

Fat Preference: A Novel Model of Eating Behavior in Rats
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Biased histamine signaling selectively gates fat preference.

Yanrong Zheng1, Jie Liao2, Zhuowen Fang3

  • 1Zhejiang Key Laboratory of Neuropsychopharmacology, School of Pharmaceutical Sciences, First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China.

Neuron
|November 27, 2025
PubMed
Summary

Scientists discovered a specific brain circuit in the paraventricular thalamus (PVT) that controls high-fat-diet (HFD) preference. The histamine H3 receptor (H3R) on PVT neurons is key to regulating fat consumption.

Keywords:
biased GPCR signalingfat preferencehistamine H3 receptorparaventricular thalamussugar preference

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Area of Science:

  • Neuroscience
  • Dietary Science
  • Molecular Biology

Background:

  • Dietary fat presents challenges in healthy eating due to its palatability and energy density.
  • Understanding molecular mechanisms for regulating fat preference is crucial for dietary management.

Purpose of the Study:

  • To identify specific neuronal populations and molecular targets involved in regulating high-fat-diet (HFD) preference.
  • To investigate the role of the paraventricular thalamus (PVT) in controlling fat consumption.

Main Methods:

  • Neuronal activity-dependent labeling to distinguish diet-responsive neurons.
  • Translating ribosome affinity purification sequencing and in situ hybridization to identify molecular markers.
  • Manipulation of histamine H3 receptor (H3R) expression and histaminergic pathways in the PVT.
  • Electrophysiological analyses to assess neuronal activity and signaling pathways.

Main Results:

  • A distinct separation was observed between HFD- and high-sugar-diet (HSD)-responsive neuronal populations in the PVT.
  • The histamine H3 receptor (H3R) was identified as a marker for HFD-responsive PVT neurons (PVT HFD).
  • Modulating H3R in the PVT specifically altered HFD consumption, indicating its role in regulating fat intake.
  • Histamine-mediated H3R activation enhanced PVT HFD neuronal excitability through G12/13 signaling.

Conclusions:

  • The PVT plays a significant role in gating fat preference.
  • The H3R-G12/13 signaling axis in the PVT represents a novel target for controlling fat consumption.