Heterozygous depletion of pik3r1 improves growth and feed conversion efficiency in Gibel carp (Carassius gibelio)

Phosphatidylinositol 3-kinase (PI3K) signaling plays an indispensable role in vertebrate metabolism and energy homeostasis. Heterozygous disruption of P85α, a PI3K subunit encoded by the pik3r1 gene, is known to improve insulin sensitivity in mammals. However, there is no direct evidence on the effects of altered expression of pik3r1 on metabolism and somatic growth in teleosts. In this study, the effects of heterozygous disruption of pik3r1 on metabolism and somatic growth in Gibel carp were investigated. Enhancement of the PI3K/AKT/mTOR signaling pathway was achieved by inducing haploinsufficiency of P85α in heterozygous pik3r1 -deficient Gibel carp. Unlike in mammalian models, there was no significant changes in the plasma glucose levels and hepatic glucose uptake. However, significant reduction in the levels of plasma triglycerides (TG), hepatic TG, amino acids, and lactate was observed. Furthermore, the haploinsufficiency of P85α significantly improved somatic growth, lipid utilization, and feed conversion efficiency (FCE) in the mutant Gibel carp. Taken together, our results demonstrate that enhancement of the PI3K/AKT/mTOR signaling pathway could effectively improve somatic growth and FCE in practical aquaculture. Therefore, genetic engineering for partial activation of the PI3K signaling pathway may be a potential breeding strategy for improvement of the traits of cultured fish in the future. • Heterozygous pik3r1 targeting in gibel carp enhanced PI3K and mTOR activity. • Improved somatic growth and feed conversion efficiency (FCE) were achieved in heterouzygous pik3r1 mutant gibel carp. • In pik3r1 mutant fish, reduction in hepatic lipid content has been achieved under regular- and even over-feeding conditions.