CHARACTERIZATION OF GHRELIN/GHSR SYSTEM ROLE IN A 60% CALORIC RESTRICTION PROTOCOL

DANIELA CASSANO; MARIA PAULA CORNEJO; GIMENA FERNANDEZ; DANIEL CASTROGIOVANNI; MARIO PERELLO

Córdoba

Congreso; XXXIV Reunión Anual SAN 2019; 2019

The hormone ghrelin is essential to cope energy deficit conditions, when plasma ghrelin levels increase and activate central functions that help to maintain glycaemia and increase appetite. These ghrelin actions are mainly mediated by the agouti-related protein (AgRP)-producing neurons of the arcuate nucleus (ARCAgRP neurons). Here, we hypothesized that up-regulation of the ghrelin system in calorie restricted (CR) mice promotes morphological remodeling of the ARCAgRP neurons that, in turn, would impact on the compensatory refeeding response after the CR period. First, we characterized a 60% caloric restriction protocol in wild-type (WT) mice. We found that CR WT mice lost 25% of their body weight after 5-day of CR, and that displayed a 5-day compensatory hyperphagia after refeeding. As compared to ad libitum fed mice, CR mice showed 1) higher plasma ghrelin levels, 2) higher density of AgRP+ fibers in several brain areas and 3) a matched increase of the levels of the marker of neuronal activation c-Fos in those brain areas. To test if these effects require the presence of the ghrelin receptor (GHSR), we studied CR GHSR-deficient mice. We found that CR GHSR-deficient mice lost ~25% of BW after 5-day 60% CR, similar as seen in WT mice, but showed a significantly smaller compensatory hyperphagia after refeeding. Thus, we conclude that ghrelin/GHSR system is involved in the regulation of the compensatory hyperphagia in CR mice.