Location: Cool and Cold Water Aquaculture Research
Title: Compensatory Response of the Somatotropic Axis from IGFBP-2b Gene Editing in Rainbow TroutAuthor
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Cleveland, Beth |
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HABARA, SHIORI - Hokkaido University |
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OKAWA, JIN - Hokkaido University |
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Radler, Lisa |
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SHIMIZU, MUNETAKA - Hokkaido University |
Submitted to: Aquaculture America
Publication Type: Abstract Only Publication Acceptance Date: 10/14/2021 Publication Date: N/A Citation: N/A Interpretive Summary: Technical Abstract: Insulin-like growth factor (IGF) is recognized as a central regulator of anabolic growth in vertebrates, largely due to its positive effects on muscle and bone growth. However, the majority of IGF-I is not free in circulation; approximately 99% of IGF-I is bound to IGF binding proteins (IGFBP). In addition to extending the half-life of IGF-I in serum, IGFBPs sequester IGF-I to peripheral tissues and can promote or inhibit ligand binding to surface receptors. Characterizing the functions of the IGFBPs is essential to understand the role of these proteins as regulators of IGF signaling. We used gene editing technology to edit IGFBP-2b, the most abundant IGFBP in serum that binds an estimated 80% of free IGF-I. The objective of this study is to determine how components of the IGF/IGFBP system respond to a reduction in serum IGFBP-2b abundance. Rainbow trout with gene editing-induced reductions in serum IGFBP-2b exhibit similar growth performance compared to fish without IGFBP-2b gene disruption. Editing the IGFBP-2b genes 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, the differential expression of igfbp genes supports the 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, suggesting 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. The compensatory regulation of IGF/IGFBP system genes indicates 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. |