Amylin in the amygdala is necessary and sufficient for feeding behavior control

Amylin, a pancreatic peptide, has a well-established role in feeding behavior control. Moreover, amylin analogues are already clinically utilized in patients with diabetes, and are under investigation as potential new anti-obesity pharmacotherapies. While area postrema has been recognized as a primary site for mediating amylin's satiating effects, more recent studies expanded this perspective to other brain regions, highlighting that our understanding of neural circuitry underlying actions of amylin on behavior remains incomplete. The central amygdala (CeA) recently emerged as a critical neural substrate for feeding behavior control and reward processing. We found that all components of amylin receptors (CTR, RAMP1-3) are expressed in the CeA; their potential role in physiology or behavior remains unknown. Therefore, here we investigated the potential ingestive and motivated behavior roles of amylin in the CeA of male and female rats. We found that intra-CeA delivered amylin was sufficient to acutely reduce chow intake in both sexes, with this hypophagic effect lasting longer in females. Intra-CeA amylin also potently reduced food-motivated behavior for sucrose. However, when high-fat and sucrose were offered, intra-CeA amylin selectively reduced the high-fat food intake, while sparing the sucrose intake. Pharmacological blockade of CeA amylin receptors increased food intake, but only in female rats. Virogenetic knockdown of CTR resulted in increased body weight gain in females, but not males. Our data indicate the CeA as a novel neural substrate for amylin. They reveal amylin receptors in the CeA are sufficient to alter feeding behavior in both sexes, while necessary only in females, underscoring a sex difference in the necessity of the CeA amylin signaling. National Institutes of Health R01DK129321 Huck Institutes Chair Funds (KPS) Swedish Research Council (2018-00660, to KPS) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.