# Pancreatic amylin dynamically reconfigures distributed brain networks governing appetite regulation in mice

## TL;DR

This study shows that amylin, a hormone from the pancreas, rapidly changes brain networks in mice that control appetite, and these effects depend on specific receptors.

## Contribution

The study reveals how amylin dynamically reconfigures brain networks in real time, linking it to appetite regulation and receptor dependency.

## Key findings

- Amylin triggers rapid and transient network reconfigurations in brain regions linked to satiation and sensory integration.
- Amylin's effects on brain connectivity and oscillations are absent in RAMP1/3 knockout mice, confirming receptor dependence.
- Amylin modulates low-frequency brain oscillations associated with appetite and reward circuits.

## Abstract

Obesity remains a major global health challenge, yet the brain-wide effects of hormones regulating appetite remain incompletely understood. Amylin, co-secreted with insulin by pancreatic β-cells, promotes satiation and is a promising therapeutic target for metabolic disorders. While its receptor distribution is well-characterized, its influence on large-scale neural dynamics is unknown. Here, resting-state fMRI was used to map time-resolved connectivity changes following peripheral amylin administration in wild-type (WT) and receptor activity-modifying protein 1/3 knockout (RAMP1/3 KO) mice. In WT animals, amylin triggered rapid and transient network reconfigurations, engaging canonical satiation hubs such as the area postrema and parabrachial nucleus, and extending to sensory-integrative areas including the inferior colliculus and insular cortex. Early hindbrain responses propagated to hypothalamic, thalamic, and mesolimbic circuits implicated in appetite and reward. These effects, along with amylin-driven modulation of large-scale networks and low-frequency oscillations, were absent in KO mice. The findings position amylin as a potent modulator of distributed brain circuits, offering a framework for targeted obesity treatments.

•Peripheral amylin induces rapid, transient reconfiguration of brain-wide networks in mice.•Connectivity shifts extend from hindbrain entry points to hypothalamic and reward hubs.•Amylin effects are absent in RAMP1/3 KO mice, confirming receptor dependence.•Amylin enhances slow brain oscillations linked to satiation and appetite control.

Peripheral amylin induces rapid, transient reconfiguration of brain-wide networks in mice.

Connectivity shifts extend from hindbrain entry points to hypothalamic and reward hubs.

Amylin effects are absent in RAMP1/3 KO mice, confirming receptor dependence.

Amylin enhances slow brain oscillations linked to satiation and appetite control.