Daily Rhythms in the IGF-1 System in the Liver of Goldfish and Their Synchronization to Light/Dark Cycle and Feeding Time

SIMPLE SUMMARY: Insulin-like growth factor-1 is a peptide that acts both as a hormone and growth factor that participates in several physiological processes in vertebrates. Due to its pleiotropic actions, its functionality is regulated both by its linkage to binding proteins and the signaling through specific receptors. This system may be temporally synchronized to ensure the anticipatory physiological adaptations to cyclic environmental changes. The aim of this work is to study the daily variations in the expression of these components belonging to the insulin-like growth factor-1 system in the liver of goldfish, as well as the influence of two environmental synchronizers, the light/dark cycle and a scheduled feeding time, on such rhythmicity. Both environmental cues influence the daily rhythms of expression of the components of the insulin-like growth factor-1 system, and particularly, feeding time synchronizes these rhythms. Overall, this work evidences the relevance of insulin-like growth factor-1 and its binding proteins as potential rhythmic outputs of the liver clock in fish. A scheduled mealtime plays a key role in the functional organization of the circadian system in animals. ABSTRACT: The relevance of the insulin-like growth factor-1 (IGF-1) system in several physiological processes is well-known in vertebrates, although little information about their temporal organization is available. This work aims to investigate the possible rhythmicity of the different components of the IGF-1 system (igf-1, the igf1ra and igf1rb receptors and the paralogs of its binding proteins IGFBP1 and IGFBP2) in the liver of goldfish. In addition, we also study the influence of two environmental cues, the light/dark cycle and feeding time, as zeitgebers. The hepatic igf-1 expression showed a significant daily rhythm with the acrophase prior to feeding time, which seems to be strongly dependent on both zeitgebers. Only igfbp1a-b and igfbp1b-b paralogs exhibited a robust daily rhythm of expression in the liver that persists in fish held under constant darkness or randomly fed. The hepatic expression of the two receptor subtypes did not show daily rhythms in any of the experimental conditions. Altogether these results point to the igf-1, igfbp1a-b, and igfbp1b-b as clock-controlled genes, supporting their role as putative rhythmic outputs of the hepatic oscillator, and highlight the relevance of mealtime as an external cue for the 24-h rhythmic expression of the IGF-1 system in fish.