Intermittent fasting can promote compensatory growth by regulating nutrient metabolism through IGF1-IGFBP3 in Pampus argenteus

Silver pomfret exhibits remarkable accelerated growth during re-feeding periods of intermittent fasting. To further investigate the underlying mechanisms, we established a full compensatory growth model and conducted transcriptome analyses of its liver, intestine, and muscle tissues. Based on our transcriptomes and RT-qPCR analysis, we found that genes associated with lipid and protein catabolism were up-regulated during fasting, whereas those related to lipid and protein anabolism were up-regulated during re-feeding, and we identified that the IGF1-IGFBP3 complex may play a critical role in regulating nutrient metabolism throughout this process. To test this hypothesis, we developed a fasting-recovery model using silver pomfret muscle cells and analyzed the expression of upstream and downstream genes associated with IGF1 through RT-qPCR and WB. We employed RNAi to knock down the expression levels of GHR, IGF1, IGFBP3, and IGF1R. In most experimental groups, there was no compensatory recovery of cell activity; however, partial compensatory recovery was observed specifically in siRNA-IGF1R group. The anabolism-related positive regulatory genes were up-regulated in S9R3 group compared to controls only within the NC and siRNA-IGF1R groups. These data indicates that during the process of fasting, silver pomfret first utilized carbohydrates and short-chain lipids, followed by proteins and long-chain lipids, and there is a significant accumulation of IGF1 combined with IGFBP3; Upon refeeding, the dissociation of free IGF1 from IGFBP3 stimulates anabolism in the fish without suppressing AMPK activity. This promotes rapid recovery of lipids followed by protein, ultimately inducing a compensatory growth response in the fish. This research enhances our understanding of the mechanisms driving accelerated growth in animals during re-feeding phases of intermittent fasting.