Fast-Refeeding-Induced Hyperphagia Requires Ghrelin Signaling

GIMENA FERNANDEZ; AGUSTINA CABRAL; PABLO NICOLÁS DE FRANCESCO; GUADALUPE GARCÍA ROMERO; ENRIQUE PORTIANSKY; MIRTA REYNALDO; MARIO PERELLÓ

Congreso; Sociedad Argentina de Investigación en Neurociencias, XXX Annual Meeting; 2015

Animals refed after fasting display a robust hyperphagia, which aims at restoring theenergy balance. Interestingly, hyperphagia persists even after animals have reached theirenergy needs if fasting is severe. The mechanism regulating the magnitude of thecompensatory events of hyperphagia are currently unclear. Here, we tested the long-termeating behavior of mice exposed to a fast-refeed paradigm and also analyzed the dynamicof the ghrelin system -the only known hormone able to increase food intake- under thesecircumstances. In addition, we tested the eating behavior after fast-refeeding in micelacking the ghrelin receptor. We found that previously fasted wild-type mice display asignificant increase of the total food intake that continues for 4 days after refeeding.Fasting increases both ghrelin plasma levels and the ghrelin binding in some, but not all,hypothalamic nuclei. This binding was particularly increased at the GABAergic terminalswithin the hypothalamic arcuate nucleus. Notably, ghrelin binding and sensitivity toexogenous ghrelin administration remained increased even after 4 days of refeeding. Incontrast, ghrelin receptor deficient mice exposed to a fast-refeed paradigm failed toincrease the total food intake after refeeding. We conclude that ghrelin signaling inGABAergic terminals increases under fasting and that this readjustment of the ghrelinsystem is involved in the fast-refeeding-induced hyperphagia. Supported by PICT2011-2142and PICTO2013-0065