Thyroid hormone-responsive protein mediates the response of chicken liver to fasting mainly through the cytokine-cytokine receptor interaction pathway.

1. The objective of this study was to explore the mediating role of thyroid hormone-responsive protein (THRSP) in the response of chicken liver to fasting.2. A batch of 7-d-old chicks with similar body weights were randomly divided into the control group and the fasting group (n = 10). The control group was fed ad libitum, while the test group fasted for 24 h. The liver and pectoral muscle tissues were collected. Chicken primary hepatocytes or myocytes were treated with different concentrations of thyroxine, glucose, insulin, oleic acid and palmitic acid, separately. Chicken primary hepatocytes were transfected with THRSP overexpression vector vs. empty vector, and the cells were used for transcriptome analysis. The mRNA expression of THRSP and other genes was determined by quantitative PCR.3. The expression of THRSP in chicken liver and pectoral muscle tissues was significantly inhibited by fasting (P < 0.05). In chicken primary hepatocytes, the expression of THRSP was significantly induced by thyroxine (0.25, 0.5, 1 mmol/l), glucose (50, 100 mmol/l), and insulin (20 nmol/l), and was significantly inhibited by palmitic acid (0.125, 0.25 mmol/l). In the myocytes, expression of THRSP was significantly induced by thyroxine (0.25, 0.5, 1 mmol/l), glucose (50 mmol/l) and oleic acid (0.125, 0.25 mmol/l), was significantly inhibited by insulin (5 nmol/l) and was not significantly affected by palmitic acid.4. Transcriptome analysis showed that overexpression of THRSP significantly affected the expression of 1411 DEGs, of which 1007 were up-regulated and 404 were down-regulated. The GO term and KEGG pathway enrichment analyses showed that these DEGs were mainly enriched in the interaction between cytokine and cytokine receptor and its regulation and signal transduction, cell growth and apoptosis and its regulation, immune response and retinol metabolism.5. In conclusion, the THRSP gene mediates biological effects of fasting by influencing the expressional regulation of the genes related to biological processes such as cytokine-cytokine receptor interaction, cell growth and apoptosis, immune response, retinol metabolism, including TGM2, HSD17B2, RUNX3, IRF1, ANKRD6, UPP2, IKBKE, and PYCR1 genes, in chicken liver.