The unexpected loss of the 'hunger hormone' ghrelin in true passerines: a game changer in migration physiology

Migratory birds must accumulate large amounts of fat prior to migration to sustain long flights. In passerines, the small body size limits the amount of energy stores that can be transported, and therefore birds undergo cycles of extreme fattening and rapid exhaustion of reserves. Research on these physiological adaptations was rattled by the discovery that birds have lost the main vertebrate regulator of fat deposition, leptin. Recent studies have thus focused on ghrelin, known as 'hunger hormone', a peptide secreted by the gastrointestinal tract to regulate, e.g. food intake and body mass in vertebrates. Studies on domestic species showed that, in birds, ghrelin has effects opposite to those described in mammals such as inhibiting instead of promoting food intake. Furthermore, recent studies have shown that ghrelin administration influences migratory behaviour in passerine birds. Using comparative genomics and immunoaffinity chromatography, we show that ghrelin has been lost in Eupasseres after the basic split from Acanthisitti about 50 Ma. We found that the ghrelin receptor is still conserved in passerines. The maintenance of a functional receptor system suggests that in Eupasserines, another ligand has replaced ghrelin, perhaps to bypass the feedback system that would hinder the large pre-migratory accumulation of subcutaneous fat. Migratory birds must accumulate large amounts of fat prior to migration to sustain long flights. In passerines, the small body size limits the amount of energy stores that can be transported, and therefore birds undergo cycles of extreme fattening and rapid exhaustion of reserves. Research on these physiological adaptations was rattled by the discovery that birds have lost the main vertebrate regulator of fat deposition, leptin. Recent studies have thus focused on ghrelin, known as 'hunger hormone', a peptide secreted by the gastrointestinal tract to regulate, e.g. food intake and body mass in vertebrates. Studies on domestic species showed that, in birds, ghrelin has effects opposite to those described in mammals such as inhibiting instead of promoting food intake. Furthermore, recent studies have shown that ghrelin administration influences migratory behaviour in passerine birds. Using comparative genomics and immunoaffinity chromatography, we show that ghrelin has been lost in Eupasseres after the basic split from Acanthisitti about 50 Ma. We found that the ghrelin receptor is still conserved in passerines. The maintenance of a functional receptor system suggests that in Eupasserines, another ligand has replaced ghrelin, perhaps to bypass the feedback system that would hinder the large pre-migratory accumulation of subcutaneous fat.© 2025 The Author(s).

Univ Ferrara
Universität Wien
Oulun Yliopisto
Veterinärmedizinische Universität Wien
University of Ferrara
University of Oulu