Free Standard AU & NZ Shipping For All Book Orders Over $80!
Register      Login
Animal Production Science Animal Production Science Society
Food, fibre and pharmaceuticals from animals
RESEARCH ARTICLE

Sirt1 regulates the expression of critical metabolic genes in chicken hepatocytes

Jianfeng Yu A B , Jie Li A , Sai He A , Lu Xu A , Yanping Zhang A , Honglin Jiang C , Daoqing Gong B and Zhiliang Gu A D
+ Author Affiliations
- Author Affiliations

A School of Biology and Food Engineering, Changshu Institute of Technology, No. 99, 3rd South Ring Road, Changshu, 215500, Jiangsu, PR China.

B College of Animal Science and Technology, Yangzhou University, No. 48, Wenhui East Road, YangZhou, 225009, Jiangsu, PR China.

C Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, 175 West Campus Drive, Blacksburg, 24061, VA, USA.

D Corresponding author. Email: Zhilianggu88@hotmail.com

Animal Production Science 60(11) 1381-1392 https://doi.org/10.1071/AN18606
Submitted: 19 January 2019  Accepted: 17 December 2019   Published: 7 April 2020

Abstract

Context: Studies in mammals show that SIRT1 plays an important role in many biological processes including liver metabolism through histone and non-histone deacetylation. Little is known about the function of Sirt1 in the chicken.

Aims: The current study investigated the expression pattern of Sirt1 mRNA in the chicken and its functions in the chicken liver.

Methods: In this work, we used real-time quantitative polymerase chain reaction to quantify the expression levels of Sirt1 mRNA in major chicken organs and tissue types, siRNA to knock down Sirt1 expression in primary chicken hepatocytes, RNA sequencing to identify gene-expression changes induced by Sirt1 knockdown, and analysed the function of the differentially expressed genes (DEGs) through gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes ontology analysis.

Key results: In total, 86 DEGs were found between Sirt1 knockdown and control chicken hepatocytes, of which 63 genes were downregulated and 23 genes were upregulated by Sirt1 knockdown. The Kyoto Encyclopedia of Genes and Genomes analysis showed that 24 DEGs were involved in metabolism. Seven DEGs were involved in carbohydrate and lipid metabolism.

Conclusions: The present study showed that Sirt1 regulates the expression of genes involved in carbohydrate and lipid metabolism and many other biological processes in the chicken liver.

Implications: The results of the present study imply that Sirt1 has various functions in the chicken liver and that Sirt1 plays a potentially important role in hepatic carbohydrate and lipid metabolism in the chicken.

Additional keywords: DEGs, metabolism, primary chicken hepatocytes, siRNA.


References

Aljomah G, Baker SS, Liu W, Kozielski R, Oluwole J, Lupu B, Baker RD, Zhu L (2015) Induction of CYP2E1 in non-alcoholic fatty liver diseases. Experimental and Molecular Pathology 99, 677–681.
Induction of CYP2E1 in non-alcoholic fatty liver diseases.Crossref | GoogleScholarGoogle Scholar | 26551085PubMed |

Banks AS, Kon N, Knight C, Matsumoto M, Gutierrez-Juarez R, Rossetti L, Gu W, Accili D (2008) SirT1 gain of function increases energy efficiency and prevents diabetes in mice. Cell Metabolism 8, 333–341.
SirT1 gain of function increases energy efficiency and prevents diabetes in mice.Crossref | GoogleScholarGoogle Scholar | 18840364PubMed |

Ben Sassi N, Averos X, Estevez I (2016) Technology and poultry welfare. Animals 6, 62
Technology and poultry welfare.Crossref | GoogleScholarGoogle Scholar |

Bordone L, Guarente L (2005) Calorie restriction, SIRT1 and metabolism: understanding longevity. Nature Reviews. Molecular Cell Biology 6, 298–305.
Calorie restriction, SIRT1 and metabolism: understanding longevity.Crossref | GoogleScholarGoogle Scholar | 15768047PubMed |

Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, Lin Y, Tran J, Ross SE, Mostoslavsky R, Cohen HY, Hu LS, Cheng H-L, Jedrychowski MP, Gygi SP, Sinclair DA, Alt FW, Greenberg ME (2004) Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science 303, 2011–2015.
Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase.Crossref | GoogleScholarGoogle Scholar | 14976264PubMed |

Byun HR, Kim DK, Koh JY (2011) Obesity and downregulated hypothalamic leptin receptors in male metallothionein-3-null mice. Neurobiology of Disease 44, 125–132.
Obesity and downregulated hypothalamic leptin receptors in male metallothionein-3-null mice.Crossref | GoogleScholarGoogle Scholar | 21726645PubMed |

Cao Y, Traer E, Zimmerman GA, McIntyre TM, Prescott SM (1998) Cloning, expression, and chromosomal localization of human long-chain fatty acid-CoA ligase 4 (FACL4). Genomics 49, 327–330.
Cloning, expression, and chromosomal localization of human long-chain fatty acid-CoA ligase 4 (FACL4).Crossref | GoogleScholarGoogle Scholar | 9598324PubMed |

Carnevale D, Pallante F, Fardella V, Fardella S, Iacobucci R, Federici M, Cifelli G, De Lucia M, Lembo G (2014) The angiogenic factor PlGF mediates a neuroimmune interaction in the spleen to allow the onset of hypertension. Immunity 41, 737–752.
The angiogenic factor PlGF mediates a neuroimmune interaction in the spleen to allow the onset of hypertension.Crossref | GoogleScholarGoogle Scholar | 25517614PubMed |

Chen S, Zhang W, Tang C, Tang X, Liu L, Liu C (2014) Vanin-1 is a key activator for hepatic gluconeogenesis. Diabetes 63, 2073–2085.
Vanin-1 is a key activator for hepatic gluconeogenesis.Crossref | GoogleScholarGoogle Scholar | 24550194PubMed |

Chen L, Bromberger PD, Nieuwenhuiys G, Hatti-Kaul R (2016) Redox balance in Lactobacillus reuteri DSM20016: roles of iron-dependent alcohol dehydrogenases in glucose/glycerol metabolism. PLoS One 11, e0168107
Redox balance in Lactobacillus reuteri DSM20016: roles of iron-dependent alcohol dehydrogenases in glucose/glycerol metabolism.Crossref | GoogleScholarGoogle Scholar | 28030590PubMed |

Dominy JE, Lee Y, Gerhart-Hines Z, Puigserver P (2010) Nutrient-dependent regulation of PGC-1alpha’s acetylation state and metabolic function through the enzymatic activities of Sirt1/GCN5. Biochimica et Biophysica Acta 1804, 1676–1683.
Nutrient-dependent regulation of PGC-1alpha’s acetylation state and metabolic function through the enzymatic activities of Sirt1/GCN5.Crossref | GoogleScholarGoogle Scholar | 20005308PubMed |

Erion DM, Yonemitsu S, Nie Y, Nagai Y, Gillum MP, Hsiao JJ, Iwasake T, Stark R, Weismann K, Yu XX, Murray SF, Bhanot S, Monia BO, Horvath TL, Gao Q, Samuel VT, Shulman GI (2009) SirT1 knockdown in liver decreases basal hepatic glucose production and increases hepatic insulin responsiveness in diabetic rats. Proceedings of the National Academy of Sciences, USA 106, 11288–11293.
SirT1 knockdown in liver decreases basal hepatic glucose production and increases hepatic insulin responsiveness in diabetic rats.Crossref | GoogleScholarGoogle Scholar |

Frescas D, Valenti L, Accili D (2005) Nuclear trapping of the forkhead transcription factor FoxO1 via Sirt-dependent deacetylation promotes expression of glucogenetic genes. The Journal of Biological Chemistry 280, 20589–20595.
Nuclear trapping of the forkhead transcription factor FoxO1 via Sirt-dependent deacetylation promotes expression of glucogenetic genes.Crossref | GoogleScholarGoogle Scholar | 15788402PubMed |

Golej DL, Askari B, Kramer F, Barnhart S, Vivekanandan-Giri A, Pennathur S, Bornfeldt KE (2011) Long-chain acyl-CoA synthetase 4 modulates prostaglandin E(2) release from human arterial smooth muscle cells. Journal of Lipid Research 52, 782–793.
Long-chain acyl-CoA synthetase 4 modulates prostaglandin E(2) release from human arterial smooth muscle cells.Crossref | GoogleScholarGoogle Scholar | 21242590PubMed |

Haigis MC, Guarente LP (2006) Mammalian sirtuins–emerging roles in physiology, aging, and calorie restriction. Genes & Development 20, 2913–2921.
Mammalian sirtuins–emerging roles in physiology, aging, and calorie restriction.Crossref | GoogleScholarGoogle Scholar |

Hayashida S, Arimoto A, Kuramoto Y, Kozako T, Honda S, Shimeno H, Soeda S (2010) Fasting promotes the expression of SIRT1, an NAD+-dependent protein deacetylase, via activation of PPARalpha in mice. Molecular and Cellular Biochemistry 339, 285–292.
Fasting promotes the expression of SIRT1, an NAD+-dependent protein deacetylase, via activation of PPARalpha in mice.Crossref | GoogleScholarGoogle Scholar | 20148352PubMed |

Hermier D (1997) Lipoprotein metabolism and fattening in poultry. The Journal of Nutrition 127, 805s–808s.
Lipoprotein metabolism and fattening in poultry.Crossref | GoogleScholarGoogle Scholar | 9164241PubMed |

Houtkooper RH, Canto C, Wanders RJ, Auwerx J (2010) The secret life of NAD+: an old metabolite controlling new metabolic signaling pathways. Endocrine Reviews 31, 194–223.
The secret life of NAD+: an old metabolite controlling new metabolic signaling pathways.Crossref | GoogleScholarGoogle Scholar | 20007326PubMed |

Imai S, Armstrong CM, Kaeberlein M, Guarente L (2000) Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature 403, 795–800.
Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase.Crossref | GoogleScholarGoogle Scholar | 10693811PubMed |

Jin Q, Yan T, Ge X, Sun C, Shi X, Zhai Q (2007) Cytoplasm-localized SIRT1 enhances apoptosis. Journal of Cellular Physiology 213, 88–97.
Cytoplasm-localized SIRT1 enhances apoptosis.Crossref | GoogleScholarGoogle Scholar | 17516504PubMed |

Li X (2013) SIRT1 and energy metabolism. Acta Biochimica et Biophysica Sinica 45, 51–60.
SIRT1 and energy metabolism.Crossref | GoogleScholarGoogle Scholar | 23257294PubMed |

Liu Y, Dentin R, Chen D, Hedrick S, Ravnskjaer K, Schenk S, Milne J, Meyers DJ, Cole P, Yates J Liu Y, Dentin R, Chen D, Hedrick S, Ravnskjaer K, Schenk S, Milne J, Meyers DJ, Cole P, Yates J (2008) A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange. Nature 456, 269–273.
A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange.Crossref | GoogleScholarGoogle Scholar | 18849969PubMed |

Lomb DJ, Laurent G, Haigis MC (2010) Sirtuins regulate key aspects of lipid metabolism. Biochimica et Biophysica Acta 1804, 1652–1657.
Sirtuins regulate key aspects of lipid metabolism.Crossref | GoogleScholarGoogle Scholar | 19962456PubMed |

Luo J, Nikolaev AY, Imai S, Chen D, Su F, Shiloh A, Guarente L, Gu W (2001) Negative control of p53 by Sir2alpha promotes cell survival under stress. Cell 107, 137–148.
Negative control of p53 by Sir2alpha promotes cell survival under stress.Crossref | GoogleScholarGoogle Scholar | 11672522PubMed |

Picard F,, Kurtev M, Chung N, Topark-Ngarm A, Senawong T, Machado De Oliveira R, Leid M, McBurney MW, Guarente L (2004) Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Nature 429, 771–776.

Pfluger PT, Herranz D, Velasco-Miguel S, Serrano M, Tschop MH (2008) Sirt1 protects against high-fat diet-induced metabolic damage. Proceedings of the National Academy of Sciences, USA 105, 9793–9798.
Sirt1 protects against high-fat diet-induced metabolic damage.Crossref | GoogleScholarGoogle Scholar |

Purushotham A, Schug TT, Xu Q, Surapureddi S, Guo X, Li X (2009) Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation. Cell Metabolism 9, 327–338.
Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation.Crossref | GoogleScholarGoogle Scholar | 19356714PubMed |

Purushotham A, Xu Q, Lu J, Foley JF, Yan X, Kim DH, Kemper JK, Li X (2012) Hepatic deletion of SIRT1 decreases hepatocyte nuclear factor 1alpha/farnesoid X receptor signaling and induces formation of cholesterol gallstones in mice. Molecular and Cellular Biology 32, 1226–1236.
Hepatic deletion of SIRT1 decreases hepatocyte nuclear factor 1alpha/farnesoid X receptor signaling and induces formation of cholesterol gallstones in mice.Crossref | GoogleScholarGoogle Scholar | 22290433PubMed |

Rodgers JT, Puigserver P (2007) Fasting-dependent glucose and lipid metabolic response through hepatic sirtuin 1. Proceedings of the National Academy of Sciences, USA 104, 12861–12866.
Fasting-dependent glucose and lipid metabolic response through hepatic sirtuin 1.Crossref | GoogleScholarGoogle Scholar |

Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P (2005) Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature 434, 113–118.
Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1.Crossref | GoogleScholarGoogle Scholar | 15744310PubMed |

Sasaki T, Kitamura T (2010) Roles of FoxO1 and Sirt1 in the central regulation of food intake. Endocrine Journal 57, 939–946.
Roles of FoxO1 and Sirt1 in the central regulation of food intake.Crossref | GoogleScholarGoogle Scholar | 21048357PubMed |

Smith JS, Brachmann CB, Celic I, Kenna MA, Muhammad S, Starai VJ, Avalos JL, Escalante-Semerena JC, Grubmeyer C, Wolberger C, Boeke JD (2000) A phylogenetically conserved NAD+-dependent protein deacetylase activity in the Sir2 protein family. Proceedings of the National Academy of Sciences of the United States of America 97, 6658–6663.
A phylogenetically conserved NAD+-dependent protein deacetylase activity in the Sir2 protein family.Crossref | GoogleScholarGoogle Scholar | 10841563PubMed |

Tanno M, Sakamoto J, Miura T, Shimamoto K, Horio Y (2007) Nucleocytoplasmic shuttling of the NAD+-dependent histone deacetylase SIRT1. The Journal of Biological Chemistry 282, 6823–6832.
Nucleocytoplasmic shuttling of the NAD+-dependent histone deacetylase SIRT1.Crossref | GoogleScholarGoogle Scholar | 17197703PubMed |

Tobita T, Guzman-Lepe J, Takeishi K, Nakao T, Wang Y, Meng F, Deng CX, Collin de l’Hortet A, Soto-Gutierrez A (2016) SIRT1 disruption in human fetal hepatocytes leads to increased accumulation of glucose and lipids. PLoS One 11, e0149344
SIRT1 disruption in human fetal hepatocytes leads to increased accumulation of glucose and lipids.Crossref | GoogleScholarGoogle Scholar | 26890260PubMed |

van den Berghe G (1991) The role of the liver in metabolic homeostasis: implications for inborn errors of metabolism. Journal of Inherited Metabolic Disease 14, 407–420.
The role of the liver in metabolic homeostasis: implications for inborn errors of metabolism.Crossref | GoogleScholarGoogle Scholar | 1749209PubMed |

van Diepen JA, Jansen PA, Ballak DB, Hijmans A, Hooiveld GJ, Rommelaere S, Galland F, Naquet P, Rutjes FPJT, Mensink RP, Schrauwen P, Tack CJ, Netea MG, Kersten S, Schalkwijk J, Stienstra R (2014) PPAR-alpha dependent regulation of vanin-1 mediates hepatic lipid metabolism. Journal of Hepatology 61, 366–372.
PPAR-alpha dependent regulation of vanin-1 mediates hepatic lipid metabolism.Crossref | GoogleScholarGoogle Scholar | 24751833PubMed |

Wang XG, Shao F, Wang HJ, Yang L, Yu JF, Gong DQ, Gu ZL (2013) MicroRNA-126 expression is decreased in cultured primary chicken hepatocytes and targets the sprouty-related EVH1 domain containing 1 mRNA. Poultry Science 92, 1888–1896.
MicroRNA-126 expression is decreased in cultured primary chicken hepatocytes and targets the sprouty-related EVH1 domain containing 1 mRNA.Crossref | GoogleScholarGoogle Scholar | 23776277PubMed |

Wang X, Yang L, Wang H, Shao F, Yu J, Jiang H, Han Y, Gong D, Gu Z (2014) Growth hormone-regulated mRNAs and miRNAs in chicken hepatocytes. PLoS One 9, e112896
Growth hormone-regulated mRNAs and miRNAs in chicken hepatocytes.Crossref | GoogleScholarGoogle Scholar | 25551824PubMed |

Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR, Frye RA, Mayo MW (2004) Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. The EMBO Journal 23, 2369–2380.
Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase.Crossref | GoogleScholarGoogle Scholar | 15152190PubMed |