Fatty liver haemorrhagic syndrome (FLHS) is a widespread metabolic disease in laying hens that causes a decrease in egg production and even death. Insulin resistance is a major contributor to the pathogenesis of nonalcoholic fatty liver disease. However, the relationship between FLHS and the insulin resistance mechanisms underlying FLHS is not well elucidated. Therefore, we established an FLHS model induced by feeding a high-energy low-protein diet. In the current study, we found that the fasting glucose and insulin concentrations were elevated in the FLHS group compared with the control group during the experimental period. The results of the oral glucose tolerance test (OGTT) and insulin sensitivity test (IST) showed a high level of insulin resistance in the FLHS model. InsR, 4EBP-1, Glut-1 and Glut-3 mRNA expression were decreased, and TOR, S6K1, and FOXO1 were elevated (P < 0.05). Metabolomic analysis with GC/MS identified 46 differentially expressed metabolites between these two groups, and of these, 14 kinds of metabolism molecules and 32 kinds of small metabolism molecules were decreased (P < 0.05). Further investigation showed that glucose, lipid and amino acid metabolism blocks in the progression of FLHS by GO functional and pathway analysis. Overall, these results suggest that insulin resistance participated in FLHS; comprehensively, metabolites participated in the dysregulated biological process.

To investigate the etiopathogenesis of fatty liver hemorrhagic syndrome (FLHS) and the protective effects of resveratrol (RSV) against FLHS in laying hens, 144 healthy 90-day-old laying hens were randomly divided into 4 groups including control (Con) group, high-energy low-protein (HELP) group, RSV group, and HELP + RSV group, each of which contained 36 hens with 3 replicates. Birds in the 4 groups were fed a basal diet, HELP diet, basal diet supplemented with 400 mg/kg RSV, and HELP diet supplemented with 400 mg/kg RSV. The histopathology of the ovary lesions on day 120, egg production, antioxidative function, and mRNA expression levels of inflammatory cytokines on days 40, 80, and 120 were determined. The lipid accumulation and hemorrhaging were more severe in the HELP group than those in the HELP + RSV group. The laying rate was markedly decreased in the HELP group compared with that in the Con and HELP + RSV groups. Furthermore, the malondialdehyde concentration was significantly increased (P < 0.05), while the levels of superoxide dismutase (SOD), catalase, and glutathione were significantly decreased (P < 0.05) in the HELP group compared with those in the Con and HELP + RSV groups. The mRNA levels of antioxidant genes (Nrf2, SOD-1, and HO-1) were markedly increased (P < 0.05) in the HELP + RSV group compared with those in the HELP group. In addition, the mRNA levels of inflammation-related genes (nuclear factor kappa B, tumor necrosis factor-α, IL-1β, and IL-6) were significantly increased (P < 0.05) in the HELP group compared with those in the Con and HELP + RSV groups. Collectively, these results indicate that oxidative stress and inflammation are involved in the occurrence and development of FLHS in the ovaries of laying hens, but RSV effectively attenuates oxidative stress and inflammation in hens with FLHS. Hence, RSV can be used as an effective feed additive to protect against FLHS.

Chicken gout resulting from nephropathogenic infectious bronchitis virus (NIBV) has become a serious kidney disease problem in chicken worldwide with alterations of the metabolic phenotypes in multiple metabolic pathways. To investigate the mechanisms in chicken responding to NIBV infection, we examined the global transcriptomic and metabolomic profiles of the chicken’s kidney using RNA-seq and GC–TOF/MS, respectively. Furthermore, we analyzed the alterations in cecal microorganism composition in chickens using 16S rRNA-seq. Integrated analysis of these three phenotypic datasets further managed to create correlations between the altered kidney transcriptomes and metabolome, and between kidney metabolome and gut microbiome. We found that 2868 genes and 160 metabolites were deferentially expressed or accumulated in the kidney during NIBV infection processes. These genes and metabolites were linked to NIBV-infection related processes, including immune response, signal transduction, peroxisome, purine, and amino acid metabolism. In addition, the comprehensive correlations between the kidney metabolome and cecal microbial community showed contributions of gut microbiota in the progression of NIBV-infection. Taken together, our research comprehensively describes the host responses during NIBV infection and provides new clues for further dissection of specific gene functions, metabolite affections, and the role of gut microbiota during chicken gout.