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

作者：Irmak Gezginer, Giulia Mazzini, Christelle Le Foll, Diana Kindler, Thomas A. Lutz, Daniel Razansky · 发表于：Molecular Metabolism · 年份：2025 · DOI：10.1016/j.molmet.2025.102313 · 被引用次数：3 · 研究领域：Neural dynamics and brain function、Regulation of Appetite and Obesity、Single-cell and spatial transcriptomics

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...