Abstract
The prepartal dietary energy level is tightly correlated with the degree of tissue mobilization that the animal experiences around parturition (giving birth). To better understand the link between the dry period dietary energy management and the inflammatory status around parturition, 12 multiparous Holstein cows were fed for the entire dry period either a high-wheat straw/lower-energy diet to supply at least 100 % of the calculated net energy for lactation (NEL) (control, CON) or a higher-energy diet to supply >140 % of NEL (overfed, OVE). The blood was sampled throughout the transition period for biomarker analyses. Liver tissue samples were taken on days −14, 7, 14, and 30 relative to parturition for triacylglycerol (TAG) composition and gene expression analysis. Fifty genes involved in inflammation, endoplasmic reticulum (ER), and oxidative stress, and cell cycle and growth were evaluated. Although blood biomarkers did not reveal signs of a greater inflammatory status compared with OVE, CON cows had a greater activation of the intrahepatic unfolded protein response prepartum. However, postpartum mRNA profiling indicated that the OVE group experienced a mild but sustained level of ER stress, with higher oxidative stress and impairment of antioxidant mechanisms. After parturition, inflammation-related genes were upregulated in OVE cows compared with CON. However, CON cows experienced a gradual increase in expression of key inflammatory transcription regulators up to 30 days postpartum which agreed with the lower plasma albumin and cholesterol, suggesting an inflammatory state. Data underscored that ER stress is not necessarily linked with inflammation during the peripartal period. Gene expression data also suggest that prepartum overnutrition could have negative effects on normal cell cycle activity. Overall, allowing cows to overconsume energy prepartum increased the hepatic pro-inflammatory response prepartum and up to the point of parturition. Subsequently, cows fed the lower-energy diet experienced a gradual increase in the inflammatory response. The lack of differences between groups in voluntary feed intake and lactation capacity suggests that nutritional management prepartum triggers different mechanisms that affect ER and oxidative stress along with inflammation. Although no clinical disorders were detected, these alterations expose animals to the development of immuno-metabolic disorders.
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References
Assenat E, Gerbal-Chaloin S, Larrey D et al (2004) Interleukin 1beta inhibits CAR-induced expression of hepatic genes involved in drug and bilirubin clearance. Hepatology 40(4):951–960
Bernabucci U, Ronchi B, Lacetera N, Nardone A (2005) Influence of body condition score on relationships between metabolic status and oxidative stress in periparturient dairy cows. J Dairy Sci 88(6):2017–2026
Bertoni G, Trevisi E (2013) Use of the liver activity index and other metabolic variables in the assessment of metabolic health in dairy herds. Vet Clin N Am Food Anim Pract 29(2):413–431
Bertoni G, Trevisi E, Han X, Bionaz M (2008) Effects of inflammatory conditions on liver activity in puerperium period and consequences for performance in dairy cows. J Dairy Sci 91(9):3300–3310
Bionaz M, Trevisi E, Calamari L et al (2007) Plasma paraoxonase, health, inflammatory conditions, and liver function in transition dairy cows. J Dairy Sci 90(4):1740–1750
Bionaz M, Chen S, Khan MJ, Loor JJ (2013) Functional role of PPARs in ruminants: potential targets for fine-tuning metabolism during growth and lactation. PPAR Res 2013:684159
Bradford BJ, Mamedova LK, Minton JE, Drouillard JS, Johnson BJ (2009) Daily injection of tumor necrosis factor-{alpha} increases hepatic triglycerides and alters transcript abundance of metabolic genes in lactating dairy cattle. J Nutr 139(8):1451–1456
Brewer JW, Diehl JA (2000) PERK mediates cell-cycle exit during the mammalian unfolded protein response. Proc Natl Acad Sci U S A 97(23):12625–12630
Dann HM, Morin DE, Bollero GA, Murphy MR, Drackley JK (2005) Prepartum intake, postpartum induction of ketosis, and periparturient disorders affect the metabolic status of dairy cows. J Dairy Sci 88(9):3249–3264
Dann HM, Litherland NB, Underwood JP et al (2006) Diets during far-off and close-up dry periods affect periparturient metabolism and lactation in multiparous cows. J Dairy Sci 89(9):3563–3577
Douglas GN, Rehage J, Beaulieu AD, Bahaa AO, Drackley JK (2007) Prepartum nutrition alters fatty acid composition in plasma, adipose tissue, and liver lipids of periparturient dairy cows. J Dairy Sci 90(6):2941–2959
Fang K, Fu W, Beardsley AR et al (2007) Overexpression of caveolin-1 inhibits endothelial cell proliferation by arresting the cell cycle at G0/G1 phase. Cell Cycle 6(2):199–204
Galbiati F, Volonte D, Liu J et al (2001) Caveolin-1 expression negatively regulates cell cycle progression by inducing G(0)/G(1) arrest via a p53/p21(WAF1/Cip1)-dependent mechanism. Mol Biol Cell 12(8):2229–2244
Gessner DK, Schlegel G, Ringseis R, Schwarz FJ, Eder K (2014) Up-regulation of endoplasmic reticulum stress induced genes of the unfolded protein response in the liver of periparturient dairy cows. BMC Vet Res 10:46
Graugnard DE, Bionaz M, Trevisi E et al (2012) Blood immunometabolic indices and polymorphonuclear neutrophil function in peripartum dairy cows are altered by level of dietary energy prepartum. J Dairy Sci 95(4):1749–1758
Graugnard DE, Moyes KM, Trevisi E et al (2013) Liver lipid content and inflammometabolic indices in peripartal dairy cows are altered in response to prepartal energy intake and postpartal intramammary inflammatory challenge. J Dairy Sci 96(2):918–935
Grossi P, Bertoni G, Cappelli FP, Trevisi E (2013) Effects of the precalving administration of omega-3 fatty acids alone or in combination with acetylsalicylic acid in periparturient dairy cows. J Anim Sci 91(6):2657–2666
Gupta S, Deepti A, Deegan S et al (2010) HSP72 protects cells from ER stress-induced apoptosis via enhancement of IRE1alpha-XBP1 signaling through a physical interaction. PLoS Biol 8(7):e1000410
Hotamisligil GS (2010) Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell 140(6):900–917
Huang K, Fingar DC (2014) Growing knowledge of the mTOR signaling network. Semin Cell Dev Biol. doi:10.1016/j.semcdb.2014.09.011
Hussey SE, Lum H, Alvarez A et al (2014) A sustained increase in plasma NEFA upregulates the Toll-like receptor network in human muscle. Diabetologia 57(3):582–591
Ingvartsen KL (2006) Feeding- and management-related diseases in the transition cow: physiological adaptations around calving and strategies to reduce feeding-related diseases. Anim Feed Sci Technol 126(3–4):175–213
Invernizzi G, Naeem A, Loor JJ (2012) Short communication: endoplasmic reticulum stress gene network expression in bovine mammary tissue during the lactation cycle. J Dairy Sci 95(5):2562–2566
Jing G, Wang JJ, Zhang SX (2012) ER stress and apoptosis: a new mechanism for retinal cell death. Exp Diabetes Res 2012:589589
Khan MJ, Jacometo CB, Graugnard DE et al (2014) Overfeeding dairy cattle during late-pregnancy alters hepatic PPARalpha-regulated pathways including hepatokines: impact on metabolism and peripheral insulin sensitivity. Gene Regul Syst Biol 8:97–111
Kushibiki S, Hodate K, Shingu H et al (2001) Effects of long-term administration of recombinant bovine tumor necrosis factor-alpha on glucose metabolism and growth hormone secretion in steers. Am J Vet Res 62(5):794–798
Leroy JL, Vanholder T, Van Knegsel AT, Garcia-Ispierto I, Bols PE (2008) Nutrient prioritization in dairy cows early postpartum: mismatch between metabolism and fertility? Reprod Domest Anim 43(Suppl 2):96–103
Minuti A, Ahmed S, Trevisi E, Piccioli-Cappelli F, Bertoni G, Bani P (2013) Assessment of gastrointestinal permeability by lactulose test in sheep after repeated indomethacin treatment. J Anim Sci 91(12):5646–5653
Morris DG, Waters SM, McCarthy SD et al (2009) Pleiotropic effects of negative energy balance in the postpartum dairy cow on splenic gene expression: repercussions for innate and adaptive immunity. Physiol Genomics 39(1):28–37
Moyes KM, Drackley JK, Morin DE, Loor JJ (2010) Greater expression of TLR2, TLR4, and IL6 due to negative energy balance is associated with lower expression of HLA-DRA and HLA-A in bovine blood neutrophils after intramammary mastitis challenge with Streptococcus uberis. Funct Integr Genomics 10(1):53–61
Ohoka N, Yoshii S, Hattori T, Onozaki K, Hayashi H (2005) TRB3, a novel ER stress-inducible gene, is induced via ATF4-CHOP pathway and is involved in cell death. EMBO J 24(6):1243–1255
Osorio JS, Ji P, Drackley JK, Luchini D, Loor JJ (2013) Supplemental Smartamine M or MetaSmart during the transition period benefits postpartal cow performance and blood neutrophil function. J Dairy Sci 96(10):6248–6263
Oyadomari S, Mori M (2004) Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ 11(4):381–389
Ozcan L, Tabas I (2012) Role of endoplasmic reticulum stress in metabolic disease and other disorders. Annu Rev Med 63:317–328
Palmer CN, Richardson TH, Griffin KJ, Hsu MH, Muerhoff AS, Clark JE, Johnson EF (1993) Characterization of a cDNA encoding a human kidney, cytochrome P-450 4A fatty acid omega-hydroxylase and the cognate enzyme expressed in Escherichia coli. Biochim Biophys Acta 1172(1–2):161–166
Pires JA, Delavaud C, Faulconnier Y, Pomies D, Chilliard Y (2013) Effects of body condition score at calving on indicators of fat and protein mobilization of periparturient Holstein-Friesian cows. J Dairy Sci 96(10):6423–6439
Polak P, Hall MN (2009) mTOR and the control of whole body metabolism. Curr Opin Cell Biol 21(2):209–218
Ron D, Walter P (2007) Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol 8(7):519–529
Schluchter MD, Elashoff JD (1990) Small-sample adjustments to tests with unbalanced repeated measures assuming several covariance structures. J Stat Comput Simul 37:69–87
Seo J, Osorio JS, Schmitt E et al (2014) Hepatic purinergic signaling gene network expression and its relationship with inflammation and oxidative stress biomarkers in blood from peripartal dairy cattle. J Dairy Sci 97(2):861–873
Shahzad K, Bionaz M, Trevisi E et al (2014) Integrative analyses of hepatic differentially expressed genes and blood biomarkers during the peripartal period between dairy cows overfed or restricted-fed energy prepartum. PLoS ONE 9(6):e99757
Shi X, Li X, Li D et al (2014) Beta-hydroxybutyrate activates the NF-kappaB signaling pathway to promote the expression of pro-inflammatory factors in calf hepatocytes. Cell Physiol Biochem 33(4):920–932
Sobocinski PZ, Canterbury WJ Jr (1982) Hepatic metallothionein induction in inflammation. Ann N Y Acad Sci 389:354–367
Sordillo LM, Contreras GA, Aitken SL (2009) Metabolic factors affecting the inflammatory response of periparturient dairy cows. Anim Health Res Rev 10(1):53–63
Trevisi E, Amadori M, Bakudila AM, Bertoni G (2009) Metabolic changes in dairy cows induced by oral, low-dose interferon-alpha treatment. J Anim Sci 87(9):3020–3029
Trevisi E, Amadori M, Cogrossi S et al (2012) Metabolic stress and inflammatory response in high-yielding, periparturient dairy cows. Res Vet Sci 93:695–704
Turk R, Juretić D, Gereš D et al (2008) Influence of oxidative stress and metabolic adaptation on PON1 activity and MDA level in transition dairy cows. Anim Reprod Sci 108(1):98–106
White CC, Feng Q, Cupples LA et al (2013) CYP4A11 variant is associated with high-density lipoprotein cholesterol in women. Pharmacogenomics J 13(1):44–51
Zamora M, Granell M, Mampel T et al (2004) Adenine nucleotide translocase 3 (ANT3) overexpression induces apoptosis in cultured cells. FEBS Lett 563(1–3):155–160
Zhang HH, Lipovsky AI, Dibble CC et al (2006a) S6K1 regulates GSK3 under conditions of mTOR-dependent feedback inhibition of Akt. Mol Cell 24(2):185–197
Zhang K, Shen X, Wu J et al (2006b) Endoplasmic reticulum stress activates cleavage of CREBH to induce a systemic inflammatory response. Cell 124(3):587–599
Zhou H, Liu R (2014) ER stress and hepatic lipid metabolism. Front Genet 5:112
Acknowledgments
The research was supported by Hatch funds under project ILLU-538–914, National Institute of Food and Agriculture, Washington, DC, USA, and NRI competitive grant 2007-468-35204-17758. M. Jawad Khan was supported in part by a fellowship from COMSATS Institute of Information Technology, Islamabad, Pakistan. Carolina Jacometo was supported in part by a fellowship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) from the Brazilian Ministry of Education. We gratefully acknowledge the help from the staff members at the University of Illinois Dairy Research Farm for animal handling and care.
Conflict of interest
M. Jawad Khan, Carolina B. Jacometo, Mario Vailati Riboni, Erminio Trevisi, Daniel E. Graugnard, Marcio N. Corrêa, and Juan J. Loor declare that they have no conflicts of interest.
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Khan, M.J., Jacometo, C.B., Vailati Riboni, M. et al. Stress and inflammatory gene networks in bovine liver are altered by plane of dietary energy during late pregnancy. Funct Integr Genomics 15, 563–576 (2015). https://doi.org/10.1007/s10142-015-0443-2
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DOI: https://doi.org/10.1007/s10142-015-0443-2