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

Abstract

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.

Keywords: avian genomics; bird migration; comparative genomics; gene loss.

Figure 1.

Phylogenetic tree showing the loss of ghrelin in Eupasserine birds. The figure illustrates the loss of ghrelin after Acanthisitta split from Eupasserines during the Palaeogene. While the receptor (GHS-R) is present even in Eupasserines, the ligand replacing ghrelin is still unknown. The phylogenetic tree was obtained from TimeTree (http://timetree.org/; last accessed 21 April 2023). The x-axis shows the age of the event in million years ago (Ma). Bird drawings were obtained from the Lynx Edicions’ Handbook of the Birds of the World with permission of Alada Gestió Empresarial S.L.

Figure 2.

GHS-R abundance was measured using an enzyme immunoassay in plasma of the common quail and the garden warbler. Boxplot of the concentration values for GHS-R detected in plasma samples of the common quail and the garden warbler. Given the high homology of the GHS-R sequence within avian species, the chicken anti-GHS-R antibody was sensitive and cross-reacts with both species.