Fast-refeeding-induced hyperphagia requires ghrelin signaling

FERNÁNDEZ G; CABRAL A; DE FRANCESCO N; GARCÍA ROMERO G; PORTIANSKY E; REYNALDO M; PERELLO M

Congreso; XXX Congreso anual de la Sociedad Argentina de Investigación en Neurociencias; 2015

Animals refeed after a period of fasting display a robust hyperphagia, which is aimed to restore the energy balance. Interestingly, hyperphagia persists even after animals have reached their energy needs if fasting episodes are severe. The central mechanism regulating the magnitude of the compensatory events of hyperphagia are currently unclear. Here, we evaluated the eating behavior, in a long term-fashion, of mice exposed to a fast-refeed paradigm and also analyzed the dynamic of the ghrelin system -the only known hormonal system able to increase food intake- under these circumstances. In addition, we evaluated the eating behavior after fast-refeeding in mice lacking the ghrelin receptor. We found that previously fasted wild-type mice display a significant increase of the total food intake that continues for 4 days after refeeding. Fasting increases both ghrelin plasma levels and the amount of the ghrelin receptor in some, but not all, hypothalamic nuclei. Ghrelin receptor was particularly increased at the GABAergic terminals within the hypothalamic arcuate nucleus. Notably, ghrelin receptor levels remained increased even after 4 days of refeeding, as indicated by an increase of the ghrelin binding sites in the hypothalamus and by an increased sensitivity to exogenous ghrelin administration. In contrast to wild-type mice, ghrelin receptor deficient mice exposed to a fast-refeed paradigm failed increase the total food intake after refeeding. We conclude that constitutive ghrelin signaling in GABAergic terminals increases under fasting and that this readjustment of the ghrelin system is involved in the fast-refeeding-induced hyperphagia.