Profiling growth performance, insulin-like growth factors, and IGF-binding proteins in rainbow trout lacking IGFBP-2b

Insulin-like growth factor-binding proteins (IGFBPs) regulate insulin-like growth factor (IGF) signaling, but IGFBP-specific functions are not well characterized in fishes. 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 [IGFBP-2b knockout (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 body weight and fork length, higher feed intake, and reduced feed conversion ratio compared with 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 IGFBP-2b. Total serum IGF-1 in the 2bKO line was reduced to 0.5- to 0.8-fold of the WT line, although the concentration of free serum IGF-1 was not affected. 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.NEW & NOTEWORTHY Knocking out IGFBP-2b in rainbow trout improved food intake, growth performance, and feed conversion ratio and reduced serum IGF-1 by 0.5- to 0.8-fold, without changes in the concentration of free serum IGF-1. Based on these findings, we propose that, in addition to IGFBP-2b, the 32-kDa IGFBP (putative IGFBP-2a) also serves as a major carrier of circulating IGF-1 in salmonids.