Effect of JAK-STAT pathway in regulation of fatty liver hemorrhagic syndrome in chickens

Abstract

To explore the molecular mechanisms of fatty liver hemorrhagic syndrome (FLHS) in laying hens, an experiment was conducted to reveal the difference of histopathological observation and gene expression between FLHS group and normal group. Methods: We compared the histopathological difference using hematoxylin and eosin staining, and proceeded RNA sequencing of adipose tissue to search differentially expressed genes and enriched biological processes and pathways. Then we validated the mRNA expression levels by real-time PCR and quantified protein levels in the circulation by enzyme-linked immunosorbent assay (ELISA). Results: 100 differentially expressed transcripts corresponding to 66 genes (DEGs) were identified between FLHS-affected group and normal group. Seven DEGs were significantly enriched in the immune response process and lipid metabolic process, including PLA2G5, WFIKKN2, DEGS2, PLIN3, IL6, CNTF and SOCS3. And these genes could be the targets of immune response and be involved in metabolic homeostasis during the process of FLHS in laying hens. Based on functional categories of the DEGs, we further proposed a model to explain the etiology and pathogenesis of FLHS. IL6 and SOCS3 mediate inflammatory responses and the satiety hormone of leptin, induce dysfunction of Jak-STAT signaling pathway, leading to insulin resistance and lipid metabolic disorders. Conversely, CNTF may reduce tissue destruction during inflammatory attacks and confer protection from inflammation-induced insulin resistance in FLHS chickens. A c c e p t e d A r t i c l e Conclusion: These findings highlight the therapeutic implications of targeting the JAK-STAT pathway. Inhibition of IL6 and SOCS3 and facilitation of CNTF could serve as a favorable strategy to enhance insulin action and improve glucose homoeostasis, which are of importance for treating obesity-related disorders for chickens.

Dysregulated H3K27 Acetylation Is Implicated in Fatty Liver Hemorrhagic Syndrome in Chickens

“…Fatty liver hemorrhagic syndrome-affected chickens had large, friable, and soft livers in contrast to healthy hens (Figure 1A), and the color varied from yellow to orange (Figure 1B), which is consistent with previous reports (Spurlock and Savage, 1993; Rozenboim et al, 2016;Zhu et al, 2020). Similar to the results we previously published (Zhu et al, 2020), there was no statistical difference in body weight between hens of the two groups, but the liver index of the FLHS group was significantly (P ≤ 0.01) higher than that of the healthy group (Table 1). Further, the concentrations of hepatic triglycerides (TG) and total cholesterol (TC) were much higher (P ≤ 0.01) than in healthy individuals (Table 1).…”

“…The featureCounts software (Liao et al, 2014) was used with "gene" as the feature and in strand-unaware mode. Lowly expressed genes (when the counts across 90% samples are lower than 2) were then removed, since those are usually more vulnerable to measurement errors as reported in our previous study (Zhu et al, 2020). The fragments per kilobase of transcript sequence per millions base pairs (FPKM) algorithm was used to normalize the expression of each gene.…”

“…The fragments per kilobase of transcript sequence per millions base pairs (FPKM) algorithm was used to normalize the expression of each gene. Differential expression analysis was performed using the DESeq2 R package (Love et al, 2014), and the resulting P-value was adjusted using Benjamini and Hochberg's approach for controlling false discovery rates (Zhu et al, 2020). Bioinformatics analyses were performed in R version 3.5.1 2 .…”

Transcriptomic analysis of the liver in aged laying hens with different eggshell strength

“…Moreover, it was reported that Jak-STAT signaling pathway was downregulated in the blood sample of laying hens fed with a dried olive pomace, indicating that Jak-STAT signaling pathway is also correlated with amelioration of immune responses ( Iannaccone et al, 2019 ). This pathway was also highlighted in the adipose tissue of an experiment comparing with fatty liver hemorrhagic syndrome ( FLHS ) chickens and normal chickens ( Zhu et al, 2021 ). In the current study, similar upregulation of genes related to Jak-STAT signaling pathway in the liver were observed for WES group compared with SES group.…”

Primary Broiler Hepatocytes for Establishment of a Steatosis Model

“…FLHS mostly occurs in caged layer hens during the peak period of egg production and in broiler breeders [ 1 , 2 ], which causes huge losses in the poultry industry. Many factors are considered to be possible causes of FLHS, but imbalanced nutrition is the major one [ 3 ], similar to nonalcoholic fatty liver disease (NAFLD) in humans [ 4 ]. NAFLD begins with insulin resistance, which is more common in birds than in mammals.…”