Compensatory response of the somatotropic axis from IGFBP-2b gene editing in rainbow trout (Oncorhynchus mykiss)

Authors: Cleveland, Beth; SHIORI, HABARA - Hokkaido University; JIN, OKAWA - Hokkaido University; Radler, Lisa; MUNETAKA, SHIMIZU - Hokkaido University

Submitted to: Genes
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/4/2020
Publication Date: 12/15/2020
Citation: Cleveland, B.M., Shiori, H., Jin, O., Radler, L.M., Munetaka, S. 2020. Compensatory response of the somatotropic axis from IGFBP-2b gene editing in rainbow trout (Oncorhynchus mykiss). Genes. 11, 1488. https://doi.org/10.3390/genes11121488.
DOI: https://doi.org/10.3390/genes11121488

Interpretive Summary: Insulin-like growth factor-I (IGF-I) is the primary growth-promoting hormone in fish, however its signaling capacity is highly regulated by IGF binding proteins (IGFBP). Rainbow trout have 22 IGFBP genes, the roles of which are not well characterized. In this study, gene editing techniques were used in rainbow trout to reduce levels of the most abundant IGFBP in serum (IGFBP-2b) by approximately 80%. Although growth performance was not affected in in these fish, components of the IGF/IGFBP system were differentially affected by the loss of IGFBP-2b. These findings suggest coordinated regulation of IGF/IGFBP system in a manner that maintains IGF-signaling at a level commensurate with nutrient intake. This study improved our understanding of IGF-related mechanisms affecting growth and nutrient utilization in rainbow trout.

Technical Abstract: Rainbow trout with gene editing-induced reductions in serum insulin-like growth factor binding protein (IGFBP)-2b exhibit similar growth performance compared to fish without IGFBP-2b gene disruption. The objective of this study is to determine how components of the insulin-like growth factor (IGF)/IGFBP system respond to the reduction in serum IGFBP-2b abundance. Editing the IGFBP-2b genes in rainbow trout resulted in an 83% decrease in serum IGFBP-2b in mutants. This resulted in a 35% reduction in serum IGF-I which was offset by reduced expression of hepatic Igfbp-1a2 and increased muscle Igfr-1a; these responses suggest that an increased IGF-I signaling capacity offset reductions in serum IGF-I. During feed deprivation, differential expression of Igfbp genes support attenuation of the growth inhibitory response, likely due to the further reduction in serum IGF-I that alleviated the need for an IGF-inhibitory response. Unique Igfbp expression patterns occurred during refeeding supported an enhanced IGF-I signaling capacity in controls. Collectively, these findings support that the role of IGFBP-2b is to regulate serum IGF-I concentrations. Compensatory regulation of IGF/IGFBP system genes indicate that adjustments in other IGFBP, both circulating and at the local level, maintain IGF-I signaling at a level appropriate for the nutritional state of the fish.