Animal Bioscience

Asian Australasian Association of Animal Production Societies (아세아태평양축산학회)
권호 표지
DOI QR코드

DOI QR Code

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

  • Zhu, Yaling (College of Animal Science and Technology, Jiangxi Agricultural University) ;
  • Mao, Huirong (College of Animal Science and Technology, Jiangxi Agricultural University) ;
  • Peng, Gang (College of Animal Science and Technology, Jiangxi Agricultural University) ;
  • Zeng, Qingjie (College of Animal Science and Technology, Jiangxi Agricultural University) ;
  • Wei, Qing (College of Animal Science and Technology, Jiangxi Agricultural University) ;
  • Ruan, Jiming (College of Animal Science and Technology, Jiangxi Agricultural University) ;
  • Huang, Jianzhen (College of Animal Science and Technology, Jiangxi Agricultural University)
  • Received : 2019.11.12
  • Accepted : 2020.02.10
  • Published : 2021.01.01
Download PDF
⟨ Previous Next ⟩

Abstract

Objective: To explore the molecular mechanisms of fatty liver hemorrhagic syndrome (FLHS) in laying hens, an experiment was conducted to reveal the differences in histopathological observation and gene expression between FLHS group and normal group. Methods: We compared the histopathological difference using hematoxylin and eosin staining and proceeded with 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 polymerase chain reaction and quantified protein levels in the circulation by enzyme-linked immunosorbent assay. Results: We identified 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 phospholipase A2 group V, WAP kunitz and netrin domain containing 2, delta 4-desaturase sphingolipid 2, perilipin 3, interleukin-6 (IL-6), ciliary neurotrophic factor (CNTF), and suppressor of cytokine signaling 3 (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. IL-6 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. 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.

Keywords

Acknowledgement

We are grateful to colleagues in College of Animal Science and Technology, Jiangxi Agricultural University for sample collection. This work was supported by the National Natural Science Foundation of China (No. 31960690; No. 31460648).

References

  1. Spurlock ME, Savage JE. Effect of dietary protein and selected antioxidants on fatty liver hemorrhagic syndrome induced in japanese quail. Poult Sci 1993;72:2095-105. https://doi.org/10.3382/ps.0722095
  2. Leeson EJSS. Aetiology of fatty liver syndrome in laying hens. Br Vet J 1988;144:602-9. https://doi.org/10.1016/0007-1935(88)90031-0
  3. Li J, Zhao XL, Yuan YC, et al. Dietary lysine affects chickens from local Chinese pure lines and their reciprocal crosses. Poult Sci 2013;92:1683-9. https://doi.org/10.3382/ps.2012-02865
  4. Trott KA, Giannitti F, Rimoldi G, et al. Fatty liver hemorrhagic syndrome in the backyard chicken: a retrospective histopathologic case series. Vet Pathol 2014;51:787-95. https://doi.org/10.1177/0300985813503569
  5. Rozenboim I, Mahato J, Cohen NA, Tirosh O. Low protein and high-energy diet: a possible natural cause of fatty liver hemorrhagic syndrome in caged White Leghorn laying hens. Poult Sci 2016;95:612-21. https://doi.org/10.3382/ps/pev367
  6. Galic S, Sachithanandan N, Kay TW, Steinberg GR. Suppressor of cytokine signalling (SOCS) proteins as guardians of inflammatory responses critical for regulating insulin sensitivity. Biochem J 2014;461:177-88. https://doi.org/10.1042/BJ20140143
  7. Rosen ED, Spiegelman BM. Adipocytes as regulators of energy balance and glucose homeostasis. Nature 2006;444:847-53. https://doi.org/10.1038/nature05483
  8. Neels JG, Olefsky JM. Inflamed fat: what starts the fire? J Clin Invest 2006;116:33-5. https://doi.org/10.1172/JCI27280
  9. Kishimoto T, Akira S, Narazaki M, Taga T. Interleukin-6 family of cytokines and gp130. Blood 1995;86:1243-54. https:// doi.org/10.1182/blood.V86.4.1243.bloodjournal8641243
  10. Adachi H, Murase D, Ohkubo T. Inhibitory mechanism of signal transduction through chicken leptin receptor by suppressor of cytokine signaling-3 (SOCS3). Japan Poult Sci 2013;50:262-9. https://doi.org/10.2141/jpsa.0120166
  11. Baker DH, Han Y. Ideal amino acid profile for chicks during the first three weeks posthatching. Poult Sci 1994;73:1441-7. https://doi.org/10.3382/ps.0731441
  12. Cinti S. The adipose organ: morphological perspectives of adipose tissues. Proc Nutr Soc 2001;60:319-28. https://doi.org/10.1079/PNS200192
  13. Pertea M, Kim D, Pertea GM, Leek JT, Salzberg SL. Transcriptlevel expression analysis of RNA-seq experiments with HISAT, StringTie and Ballgown. Nat Protoc 2016;11:1650-67. https://doi.org/10.1038/nprot.2016.095
  14. Liao Y, Smyth GK, Shi W. FeatureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 2014;30:923-30. https://doi.org/10.1093/bioinformatics/btt656
  15. Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 2014;15:550. https://doi.org/10.1186/s13059-014-0550-8
  16. Dobin A, Davis CA, Schlesinger F, et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 2013;29:15-21. https://doi.org/10.1093/bioinformatics/bts635
  17. McManus CJ, Duff MO, Eipper-Mains J, Graveley BR. Correction for McManus et al, Global analysis of trans-splicing in Drosophila. PNAS 2013;110:7958-9. https://doi.org/10.1073/pnas.1304972110
  18. Sato H, Taketomi Y, Ushida A, et al. The adipocyte-inducible secreted phospholipases PLA2G5 and PLA2G2E play distinct roles in obesity. Cell Metab 2014;20:119-32. https://doi.org/10.1016/j.cmet.2014.05.002
  19. Ohi K, Ursini G, Li M, et al. DEGS2 polymorphism associated with cognition in schizophrenia is associated with gene expression in brain. Transl Psychiatry 2015;5:e550. https://doi.org/10.1038/tp.2015.45
  20. Bostrom M, Kalm M, Eriksson Y, et al. A role for endothelial cells in radiation-induced inflammation. Int J Radiat Biol 2018:94:259-71. https://doi.org/10.1080/09553002.2018.1431699
  21. Stumpff F. A look at the smelly side of physiology: transport of short chain fatty acids. Pflugers Arch 2018;470:571-98. https://doi.org/10.1007/s00424-017-2105-9
  22. Monestier O, Blanquet V. WFIKKN1 and WFIKKN2: "Companion" proteins regulating TGFB activity. Cytokine Growth Factor Rev 2016;32:75-84. https://doi.org/10.1016/j.cytogfr.2016.06.003
  23. Shepherd SO, Cocks M, Meikle PJ, et al. Lipid droplet remodelling and reduced muscle ceramides following sprint interval and moderate-intensity continuous exercise training in obese males. Int J Obes (Lond) 2017;41:1745-54. https://doi.org/10.1038/ijo.2017.170
  24. Biswas S, Adrian M, Evdokimov K, et al. Counter-regulation of the ligand-receptor pair Leda-1/Pianp and Pilrα during the LPS-mediated immune response of murine macrophages. Biochem Biophys Res Commun 2015;464:1078-83. https://doi.org/10.1016/j.bbrc.2015.07.079
  25. Taddeo EP, Hargett SR, Lahiri S, et al. Lysophosphatidic acid counteracts glucagon-induced hepatocyte glucose production via STAT3. Sci Rep 2017;7:127. https://doi.org/10.1038/s41598-017-00210-y
  26. Wilkinson TS, Roghanian A, Simpson AJ, Sallenave J-M. WAP domain proteins as modulators of mucosal immunity. Biochem Soc Trans 2011;39:1409-15. https://doi.org/10.1042/BST0391409
  27. Wirth TC, Xue HH, Rai D, et al. Repetitive antigen stimulation induces stepwise transcriptome diversification but preserves a core signature of memory CD8(+) T cell differentiation. Immunity 2010;33:128-40. https://doi.org/10.1016/j.immuni.2010.06.014
  28. Rowe ER, Mimmack ML, Barbosa AD, et al. Conserved amphipathic helices mediate lipid droplet targeting of perilipins 1-3. J Biol Chem 2016;291:6664-78. https://doi.org/10.1074/jbc.M115.691048
  29. Nonogaki K, Pan XM, Moser AH, et al. LIF and CNTF, which share the gp130 transduction system, stimulate hepatic lipid metabolism in rats. Am J Physiol Endocrinol Metab 1996;271:E521-8. https://doi.org/10.1152/ajpendo.1996.271.3.E521
  30. Watt MJ, Dzamko N, Thomas WG, et al. CNTF reverses obesity-induced insulin resistance by activating skeletal muscle AMPK. Nat Med 2006;12:541-8. https://doi.org/10.1038/nm1383
  31. O'Shea JJ, Plenge R. JAK and STAT signaling molecules in immunoregulation and immune-mediated disease. Immunity 2012;36:542-50. https://doi.org/10.1016/j.immuni.2012.03.014
  32. Gurzov EN, Stanley WJ, Pappas EG, Thomas HE, Gough DJ. The JAK/STAT pathway in obesity and diabetes. FEBS J 2016;283:3002-15. https://doi.org/10.1111/febs.13709
  33. Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 2004;89:2548-56. https://doi.org/10.1210/jc.2004-0395
  34. Yasukawa H, Ohishi M, Mori H, et al. IL-6 induces an anti-inflammatory response in the absence of SOCS3 in macrophages. Nat Immunol 2003;4:551-6. https://doi.org/10.1038/ni938
  35. Spangler JB, Moraga I, Mendoza JL, Garcia KC. Insights into cytokine-receptor interactions from cytokine engineering. Annu Rev Immunol 2015;33:139-67. https://doi.org/10.1146/annurev-immunol-032713-120211
  36. Wang B, Charukeshi Chandrasekera P, Pippin JJ. Leptin- and leptin receptor-deficient rodent models: relevance for human type 2 diabetes. Curr Diabetes Rev 2014;10:131-45. https://doi.org/10.2174/1573399810666140508121012

Cited by

  1. Dysregulated H3K27 Acetylation Is Implicated in Fatty Liver Hemorrhagic Syndrome in Chickens vol.11, 2021, https://doi.org/10.3389/fgene.2020.574167
  2. A novel chicken model of fatty liver disease induced by high cholesterol and low choline diets vol.100, pp.3, 2021, https://doi.org/10.1016/j.psj.2020.11.046