243 | Agouti-related protein-expressing neurons mediate enhanced saccharine intake in calorie restricted male mice

Neuroendocrinology and Neuroimmunology

Author: Daniela Alejandra Cassano | Email: danicassano@hotmail.com

Daniela Cassano , Franco Barrile , Mirta Reynaldo , Nathalia Ferreira , María Paula Cornejo , Higor Fideles Silva , Matías Ezequiel Cure , Rodrigo Rorato , Helgi Schioth , Mario Perelló 1°3°

1° Laboratory of Neurophysiology of the Multidisciplinary Institute of Cell Biology (IMBICE) (CONICET – CIC-PBA – UNLP). La Plata, Argentina.
2° Department of Biophysics, Paulista Medical School, Federal University of Sao Paulo. São Paulo, Brasil
3° Department of Surgical Sciences, Functional Pharmacology and Neuroscience, University of Uppsala. Uppsala, Sweden

Animals under calorie restriction (CR) display enhanced reward-related behaviors towards palatable stimuli, and the molecular basis underlying such adaptations remain uncertain. Agouti-related protein (AgRP)-expressing neurons, located in the arcuate nucleus (ARH), are able to sense circulating factors. AgRP neurons are activated under energy deficit condition, such as CR, and the connection between AgRP neurons and reward-related behaviours is established. We studied if AgRP neurons orchestrate the enhancement of reward-related behaviours observed in mice under CR. Male mice were fed with the 40% of their daily food intake for 5 days and were also exposed to a non-caloric sweetener solution, saccharine, for 4 hours before each meal. Wildtype mice under CR showed an increase of saccharine intake. Using an ARH ablated mouse model, we found that the ARH integrity was required for CR-induced enhancement of saccharine intake. The use of Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to selectively inhibit AgRP neurons led to a reduction of CR-induced enhancement of saccharine intake. Conversely, excitatory DREADDs selectively in AgRP neurons showed that activation of AgRP neurons alone was sufficient to induce saccharine intake in ad libitum fed mice. In conclusion, AgRP neurons activation is required for enhanced saccharine intake in CR, and sufficient to induce saccharine intake in fed mice.