Transcriptome analysis reveals IGF-dependent and IGF-independent mechanisms affected by loss of IGF binding protein-2b in rainbow trout

In teleosts, insulin-like growth factor binding protein-2b (IGFBP-2b) is the major carrier of serum insulin-like growth factor (IGF). A line of gene edited rainbow trout (2bKO) was produced that lack a functional IGFBP-2b and associated phenotypes of reduced serum IGF-1, increased appetite, and faster growth compared to wild type controls (WT). Transcriptomic analysis was completed in liver and muscle from fed and feed deprived fish from the 2bKO and WT line; the DEG profiles were used to identify biological functions and pathways affected by the loss of IGFBP-2b and predict IGF-dependent and IGF-independent mechanisms regulated by IGFBP-2b. In general, DEGs reflected down-regulation of hepatic functions and signaling pathways in 2bkO liver, while an overall up-regulation was observed in muscle. A predicted increase in IGF-1 signaling in muscle of fed fish likely facilitated an up-regulation in myogenic mechanisms. IGF-independent responses in both liver and muscle are consistent with IGFBP-2b interacting with Type II, III, and IV nuclear receptors such as HNF4A, THR, LXR, and PXR, thus mediating changes in lipid, glucose, and sterol metabolism. In liver, immune and cytokine systems were inhibited (TNF-a, NF-kB, IL-1B), supporting that IGFBP-2b may play a central role to regulate the crosstalk between systems that modulate the balance of energy between growth and immune function. In summary, through both enhanced IGF-1 signaling and regulation of IGF-independent mechanisms, it is predicted that the loss of IGFBP-2b increased muscle growth and regulated nutrient metabolism and cytokine signaling, providing insight into the functional role of IGFBP-2b in rainbow trout.