Goose Hepatic IGFBP2 Is Regulated by Nutritional Status and Participates in Energy Metabolism Mainly through the Cytokine-Cytokine Receptor Pathway

Simple Summary Nutritional shortages or oversupply, such as fasting, restricted feeding, or overfeeding, often occur during animal production. Changes in nutritional status significantly affect animal health and production performance. Although the effect of nutritional changes on the expression of insulin-like growth factor-binding protein 2 (IGFBP2) in the liver is well established, the specific role of IGFBP2 in the response of the goose liver to these changes remains unclear. Further investigations are required to fully understand the involvement of IGFBP2 in this process. To address this, we used two types of animal models: the fasting/refeeding and overfeeding models of geese for in vivo study, and cultured goose primary hepatocytes for in vitro study. Data indicate that IGFBP2 expression in the goose liver was induced by fasting, but inhibited by refeeding and overfeeding. IGFBP2 overexpression in goose primary hepatocytes mainly inhibited the expression of the genes in the cytokine-cytokine receptor pathway, which was partly validated in in vitro models. These findings suggest that IGFBP2 mediates the response of the goose liver to changes in nutritional status, mainly through the cytokine-cytokine receptor pathway. Changes in the nutritional status of animals significantly affect their health and production performance. However, it is unclear whether insulin-like growth factor-binding protein 2 (IGFBP2) mediates these effects. This study aimed to investigate the impact of changes in nutritional and energy statuses on hepatic IGFBP2 expression and the mechanism through which IGFBP2 plays a mediating role. Therefore, the expression of IGFBP2 was first determined in the livers of fasting/refeeding and overfeeding geese. The data showed that overfeeding inhibited IGFBP2 expression in the liver compared with the control (normal feeding) group, whereas the expression of IGFBP2 in the liver was induced by fasting. Interestingly, the data indicated that insulin inhibited the expression of IGFBP2 in goose primary hepatocytes, suggesting that the changes in IGFBP2 expression in the liver in the abovementioned models may be partially attributed to the blood insulin levels. Furthermore, transcriptome sequencing analysis showed that the overexpression of IGFBP2 in geese primary hepatocytes significantly altered the expression of 337 genes (including 111 up-regulated and 226 down-regulated genes), and these differentially expressed genes were mainly enriched in cytokine-cytokine receptor, immune, and lipid metabolism-related pathways. We selected the most significant pathway, the cytokine-cytokine receptor pathway, and found that the relationship between the expression of these genes and IGFBP2 in goose liver was in line with the findings from the IGFBP2 overexpression assay, i.e., the decreased expression of IGFBP2 was accompanied by the increased expression of LOC106041919, CCL20, LOC106042256, LOC106041041, and IL22RA1 in the overfed versus normally fed geese, and the increased expression of IGFBP2 was accompanied by the decreased expression of these genes in fasting versus normally fed geese, and refeeding prevented or attenuated the effects of fasting. The association between the expression of these genes and IGFBP2 was verified by IGFBP2-siRNA treatment of goose primary hepatocytes, in which IGFBP2 expression was induced by low serum concentrations. In conclusion, this study suggests that IGFBP2 mediates the biological effects induced by changes in nutritional or energy levels, mainly through the cytokine-cytokine receptor pathway.