201-OR: Circadian Control of Feeding by Amygdala PKR2 Neurons

Résumé fourni par la source

Introduction and Objective: Despite recent advancements in weight loss therapeutics, obesity still remains an epidemic. Discovery of new weight loss targets is needed to develop more diverse treatments with fewer side effects and better accessibility. In this study, we identify Prokineticin receptor 2 (PKR2) in amygdala neurons as a key regulator or food intake, establish its modulation by MRAP2, and map their neuronal inputs. Methods: We used genetic and viral tools to delete PKR2 and MRAP2, as well as to express neuronal tracers, reporters, and DREADDs in the mouse brain. Food intake was measured with either Fed3 or Biodaq. Fiber photometry was used to measure neuronal activity. Results: Deletion of PKR2 from the amygdala resulted in an increase in food intake, especially in female mice. This hyperphagia was exclusively observed during the light cycle, suggesting that PKR2 contributes to the determination of feeding periods. This is consistent with our observation that the activity of amygdala PKR2 neurons, recorded by fiber photometry, oscillates over a 24-hour period with its highest activity at ZT-6 (12:00 pm) and lowest at ZT-18 (12:00 am). Retrograde tracing experiments identify several putative brain areas in which neurons expressing the PKR2 agonist prokineticin-2 (PK2) project to amygdala PKR2 neurons and may be involved in the regulation of feeding. Conclusion: We showed PKR2 in amygdala neurons plays a critical role in the control of daytime feeding in rodents, especially within females. We identified multiple brain areas containing PK2-expressing neurons that project to amygdala PKR2 neurons, establishing the neuronal network involved in prokineticin peptides’ control over feeding. Disclosure K. Bowman: None. A. Mittal: None. J. Sebag: None.

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