Profiling growth performance and insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) in fed and feed deprived rainbow trout lacking IGFBP-2b

Authors: Cleveland, Beth; IZUTSU, AYAKA - Hokkaido University; USHIZAWA, YUIKA - Hokkaido University; Radler, Lisa; SHIMIZU, MUNETAKA - Hokkaido University

Submitted to: American Journal of Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/9/2024
Publication Date: N/A
Citation: N/A

Interpretive Summary: Insulin-like growth factor (IGF)-1 is an anabolic hormone that circulates in blood and promotes growth of muscle and bone tissue. Insulin-like growth factor binding proteins (IGFBP) regulate IGF signaling, but IGFBP-specific functions are not well characterized in fish. Therefore we used gene editing to generate a loss-of-function model to define the functional role of IGFBP-2b, the major carrier of IGF-1 in serum. Knocking out IGFBP-2b in rainbow trout improved food intake, growth performance, and feed conversion ratio and reduced total serum IGF-1, without impacts on the concentration of free serum IGF-1. Based on these findings we propose that both IGFBP-2a and IGFBP-2b serve as major carriers of circulating IGF-1 in salmonids. Collectively, these findings advance understanding of the role of IGFBPs as carriers of circulating IGF-1 and their significance as regulators of growth in fish.

Technical Abstract: Insulin-like growth factor binding proteins (IGFBP) regulate insulin-like growth factor (IGF) signaling, but IGFBP-specific functions are not well characterized in fish. A line of rainbow trout (Oncorhynchus mykiss) lacking a functional IGFBP-2b was produced using gene editing and subsequent breeding to an F2 generation. This loss-of-function model (2bKO) was subjected to either continuous feeding or feed deprivation (3 wk) followed by refeeding (1 wk). During continuous feeding, the 2bKO line displayed faster specific growth rate for both biomass and fork length, higher feed intake, and reduced feed conversion ratio compared to a wild type (WT) line. However, loss of IGFBP-2b did not affect the feed deprivation or refeeding response in terms of weight loss or weight gain, respectively. Several components of the IGF/IGFBP system were affected by loss of IGFBP2b. Total serum IGF-1 in the 2bKO line was reduced to 0.5 – 0.8-fold of the WT line although the concentration of free serum IGF-1 was similar. Serum IGFBP-1b was reduced in 2bKO fish to less than 0.5-fold of WT levels. Gene expression differences include reduced abundance of igfbp1a1, igfbp1b2, igfbp5b2, and igfbp6b1 transcripts, and elevated igf2 and igfbp6b2 transcripts in liver of the 2bKO line. Collectively, these findings suggest that although IGFBP-2b is a carrier of circulating IGF-1 in salmonids, the presence of IGFBP-2a and compensatory responses of other IGF/IGFBP system components support an anabolic response that improved growth performance in the loss-of-function model.