From the pancreas to the amygdala: New brain area critical for ingestive and motivated behavior control exerted by amylin

Amylin, a pancreatic peptide, has a well-established role in feeding behavior control. Amylin analogues are clinically utilized in patients with diabetes and are under investigation as potential anti-obesity pharmacotherapies. The neural circuits underlying actions of amylin on behavior are not well understood. While amylin was found to bind to the central amygdala (CeA) of rodents and primates and we found that all components of amylin receptors are present in the CeA, their potential role in physiology or behavior remains unknown. Here, we investigated the impact of this potential pancreas – CeA amylin-mediated communication – on ingestive and motivated behaviors. Activation of CeA amylin receptors resulted in a robust hypophagia, reduced food-motivated behavior, and altered macronutrient preference in male and female rats. Clinically used amylin analogue, pramlintide, reduced meal size and frequency by acting on the CeA. Disruption of CeA amylin signaling led to hyperphagia and body weight gain in a sex divergent manner. Importantly, CeA amylin signaling was required for appetite suppression induced by peripherally applied amylin, highlighting translational relevance of this brain site. Our data indicate the CeA is a critical neural substrate for amylin signaling.