Skip to main content

Advertisement

Log in

The effect of aspartate on the energy metabolism in the liver of weanling pigs challenged with lipopolysaccharide

  • Original Contribution
  • Published:
European Journal of Nutrition Aims and scope Submit manuscript

Abstracts

Purpose

This study was conducted to investigate whether aspartate (Asp) could improve liver energy status in the lipopolysaccharide (LPS)-challenged pigs.

Methods

Twenty-four weaned pigs were assigned to four treatments: (1) nonchallenged control (control diet and saline-treated); (2) LPS-challenged control (the same control diet and LPS-challenged); (3) LPS + 0.5 % Asp treatment (0.5 % Asp diet and LPS-challenged); and (4) LPS + 1.0 % Asp treatment (a 1.0 % Asp diet and LPS-challenged). On d 19, the pigs were injected intraperitoneally with Escherichia coli LPS at 100 μg/kg body weight, and the same volume of 0.9 % NaCl solution, respectively. All pigs were slaughtered at 24 h after LPS or saline injection, and the liver was collected for further analysis.

Results

Dietary supplementation with Asp improved liver energy status evidenced by the increased ATP concentration and adenylate energy charges, and the decreased AMP concentration and AMP/ATP ratio (p < 0.05). Asp supplementation increased the mRNA expression of key enzymes in hepatic glycolysis and tricarboxylic acid (TCA) cycle, including pyruvate kinase and citrate synthase (p < 0.05), and had a tendency to increase hepatic pyruvate dehydrogenase and isocitrate dehydrogenase β mRNA expression (p < 0.10). In addition, Asp increased the mRNA expressions of hepatic AMP-activated protein kinase (AMPK) α1, AMPKα2, silent information regulator (Sirt1), and proliferator-activated receptor-γ coactivator 1α (PGC1α) (p < 0.05). Moreover, Asp increased AMPKα phosphorylation (p < 0.05).

Conclusions

These results indicated that dietary supplementation of Asp could improve energy status in LPS-injured liver, which might result from motivating the metabolism pathway of TCA cycle and glycolysis and stimulating the AMPK signaling pathway.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Garg A (2000) Lipodystrophies. Am J Med 108:143–152

    Article  CAS  Google Scholar 

  2. Fox CJ, Hammerman PS, Thompson CB (2005) Fuel feeds function: energy metabolism and the T-cell response Nat. Rev Immunol 5:844–852

    Article  CAS  Google Scholar 

  3. McBride BW, Kelly JM (1990) Energy cost of absorption and metabolism in the ruminant gastrointestinal tract and liver: a review. J Anim Sci 68:2997–3010

    CAS  Google Scholar 

  4. Alipour M, Omri A, Smith MG, Suntres ZE (2007) Prophylactic effect of liposomal N-acetylcysteine against LPS-induced liver injuries. J Endotoxin Res 13:297–304

    Article  CAS  Google Scholar 

  5. Giannone PJ, Nankervis CA, Richter JM, Schanbacher BL, Reber KM (2009) Prenatal lipopolysaccharide increases postnatal intestinal injury in a rat model of necrotizing enterocolitis. J Pediatr Gastroenterol Nutr 48:276–282

    Article  CAS  Google Scholar 

  6. Marsin AS, Bertrand L, Rider MH, Deprez J, Beauloye C, Vincent MF, Van den Berghe G, Carling D, Hue L (2000) Phosphorylation and activation of heart PFK-2 by AMPK has a role in the stimulation of glycolysis during ischaemia. Curr Biol 10:1247–1255

    Article  CAS  Google Scholar 

  7. Sambandam N, Lopaschuk GD (2003) AMP-activated protein kinase (AMPK) control of fatty acid and glucose metabolism in the ischemic heart. Prog Lipid Res 42:238–256

    Article  CAS  Google Scholar 

  8. Musi N, Hirshman MF, Arad M, Xing Y, Fujii N, Pomerleau J, Ahmad F, Berul CI, Seidman JG, Tian R, Goodyear LJ (2005) Functional role of AMP-activated protein kinase in the heart during exercise. FEBS Lett 579:2045–2050

    Article  CAS  Google Scholar 

  9. Hardie DG (2007) AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol 8:774–785

    Article  CAS  Google Scholar 

  10. Russell RR, Taegtmeyer H (1991) Changes in citric acid cycle flux and anaplerosis antedate the decline in isolated rat hearts utilizing acetoacetate. J Clin Invest 87:384–390

    Article  CAS  Google Scholar 

  11. Rosenfeldt FL, Korchazhkina OV, Richards SM, Fisher JL, Tong S, Pisarenko OI (1998) Aspartate improves recovery of the recently infarcted rat heart after cardioplegic arrest. Eur J Cardiothorac Surg 14:185–190

    Article  CAS  Google Scholar 

  12. Yudkoff M, Nelson D, Daikhin Y, Erecińska M (1994) Tricarboxylic acid cycle in rat brain synaptosomes. Fluxes and interactions with Aspartate aminotransferase and malate/Aspartate shuttle. J Biol Chem 269:27414–27420

    CAS  Google Scholar 

  13. Leng WB, Liu YL, Shi HF, Li S, Zhu HL, Pi DA, Hou YQ, Gong J (2014) Aspartate alleviates liver injury and regulates mRNA expressions of TLR4 and NOD signaling related genes in weaned pigs after lipopolysaccharide challenge. J Nutr Biochem 25:592–599

    Article  CAS  Google Scholar 

  14. Pi DA, Liu YL, Shi HF, Li S, Odle J, Lin X, Zhu H, Chen F, Hou Y, Leng W (2014) Dietary supplementation of aspartate enhances intestinal integrity and energy status in weanling piglets after lipopolysaccharide challenge. J Nutr Biochem 25:456–462

    Article  CAS  Google Scholar 

  15. Li Q, Liu YL, Che ZQ, Zhu H, Meng G, Hou Y, Ding B, Yin Y, Chen F (2012) Dietary l-arginine supplementation alleviates liver injury caused by Escherichia coli LPS in weaned pigs. Innate Immun 18:804–814

    Article  Google Scholar 

  16. Chen F, Liu YL, Zhu HL, Hong Y, Wu Z, Hou Y, Li Q, Ding B, Yi D, Chen H (2013) Fish oil attenuates liver injury caused by LPS in weaned pigs associated with inhibition of TLR4 and NOD signaling pathways. Innate Immun 19:504–515

    Article  Google Scholar 

  17. NRC (1998) Nutrient requirements of Swine, 10th edn. National Academic Press, Washington

    Google Scholar 

  18. Hou Y, Yao K, Wang L, Ding B, Fu D, Liu Y, Zhu H, Liu J, Li Y, Kang P, Yin Y, Wu G (2011) Effects of α-ketoglutarate on energy status in the intestinal mucosa of weaned piglets chronically challenged with lipopolysaccharide. Br J Nutr 106:357–363

    Article  CAS  Google Scholar 

  19. Liu Y, Chen F, Odle J, Lin X, Jacobi SK, Zhu H, Wu Z, Hou Y (2012) Fish oil enhances intestinal integrity and inhibits TLR4 and NOD2 signaling pathways in weaned pigs after LPS challenge. J Nutr 142:2017–2024

    Article  CAS  Google Scholar 

  20. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and 2−ΔΔCT method. Methods 25:402–408

    Article  CAS  Google Scholar 

  21. Hardie DG, Hawley SA (2001) AMP-activated protein kinase: the energy charge hypothesis revisited. BioEssays 23:1112–1119

    Article  CAS  Google Scholar 

  22. Sivakumar R, Anandh Babu PV, Shyamaladevi CS (2008) Protective effect of Aspartate and glutamate on cardiac mitochondrial function during myocardial infarction in experimental rats. Chem Biol Interact 176:227–233

    Article  CAS  Google Scholar 

  23. Wolf A, Agnihotri S, Micallef J, Mukherjee J, Sabha N, Cairns R, Hawkins C, Guha A (2011) Hexokinase 2 is a key mediator of aerobic glycolysis and promotes tumor growth in human glioblastoma multiforme. J Exp Med 208:313–326

    Article  CAS  Google Scholar 

  24. Currie PD, Sullivan DT (1994) Structure and expression of the gene encoding phosphofructokinase (PFK) in Drosophila melanogaster. J Biol Chem 269:24679–24687

    CAS  Google Scholar 

  25. Zanella A, Bianchi P, Baronciani L, Zappa M, Bredi E, Vercellati C, Alfinito F, Pelissero G, Sirchia G (1997) Molecular characterization of PK-LR gene in pyruvate kinase-deficient Italian patients. Blood 89:3847–3852

    CAS  Google Scholar 

  26. Tessier JP, Thurner B, Jüngling E, Lückhoff A, Fischer Y (2003) Impairment of glucose metabolism in hearts from rats treated with endotoxin. Cardiovasc Res 60:119–130

    Article  CAS  Google Scholar 

  27. Shands JW Jr, Miller V, Martin H, Senterfitt V (1969) Hypoglycemic activity of endotoxin. II. Mechanism of the phenomenon in BCG-infected mice. J Bacteriol 98:494–501

    CAS  Google Scholar 

  28. MacDonald MJ, Brown LJ, Longacre MJ, Stoker SW, Kendrick MA, Hasan NM (2013) Knockdown of both mitochondrial isocitrate dehydrogenase enzymes in pancreatic beta cells inhibits insulin secretion. Biochim Biophys Acta 1830:5104–5111

    Article  CAS  Google Scholar 

  29. Schanbacher FL, Willett LB, Moorehead PD (1981) Ornithine decarboxylase, serum isocitrate dehydrogenase and clinical chemistry changes during thioacetamide-induced hepatotoxicity in a calf. J Anim Sci 53:1658–1670

    CAS  Google Scholar 

  30. Feingold KR, Moser A, Patzek SM, Shigenaga JK, Grunfeld C (2009) Infection decreases fatty acid oxidation and nuclear hormone receptors in the diaphragm. J Lipid Res 50:2055–2063

    Article  CAS  Google Scholar 

  31. Xue B, Kahn BB (2006) AMP-activated protein kinase integrates nutrient and hormonal signals to regulate food intake and energy balance through effects in the hypothalamus and peripheral tissues. J Physiol 574:73–83

    Article  CAS  Google Scholar 

  32. Zhao X, Zmijewski JW, Lorne E, Liu G, Park YJ, Tsuruta Y, Abraham E (2008) Activation of AMPK attenuates neutrophil proinflammatory activity and decreases the severity of acute lung injury. Am J Physiol Lung Cell Mol Physiol 295:L497–L504

    Article  CAS  Google Scholar 

  33. Hardie DG, Carling D, Carlson M (1998) The AMP-activated/SNF1 protein kinase subfamily: metabolic sensors of the eukaryotic cell? Annu Rev Biochem 67:821–855

    Article  CAS  Google Scholar 

  34. Bolster DR, Crozier SJ, Kimball SR, Jefferson LS (2002) AMP-activated protein kinase suppresses protein synthesis in rat skeletal muscle through down-regulated mammalian target of rapamycin (mTOR) signaling. J Biol Chem 277:23977–23980

    Article  CAS  Google Scholar 

  35. Wijesekara N, Tung A, Thong F, Klip A (2006) Muscle cell depolarization induces a gain in surface GLUT4 via reduced endocytosis independently of AMPK. Am J Physiol Endocrinol Metab 290:E1276–E1286

    Article  CAS  Google Scholar 

  36. Guarente L (2006) Sirtuins as potential targets for metabolic syndrome. Nature 444:868–874

    Article  CAS  Google Scholar 

  37. Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P, Elliott P, Geny B, Laakso M, Puigserver P, Auwerx J (2006) Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 127:1109–1122

    Article  CAS  Google Scholar 

  38. Fernandez-Marcos PJ, Auwerx J (2011) Regulation of PGC-1a, a nodal regulator of mitochondrial biogenesis. Am J Clin Nutr 93:884S–890S

    Article  CAS  Google Scholar 

  39. Chen ZP, McConell GK, Michell BJ, Snow RJ, Canny BJ, Kemp BE (2000) AMPK signaling in contracting human skeletal muscle: acetyl-CoA carboxylase and NO synthase phosphorylation. Am J Physiol Endocrinol Metab 279:E1202–E1206

    CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by the National Natural Science Foundation of China (31372318 and 31172222), the Program for New Century Excellent Talents in University (NCET-10-0158), the National Basic Research Program of China (2012CB126305), the Project of Natural Science Foundation of Hubei Province (2010CDA050 and 2013CFA029), and the Project of International Cooperation of Hubei Province (2011BFA008).

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yulan Liu.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kang, P., Liu, Y., Zhu, H. et al. The effect of aspartate on the energy metabolism in the liver of weanling pigs challenged with lipopolysaccharide. Eur J Nutr 54, 581–588 (2015). https://doi.org/10.1007/s00394-014-0739-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-014-0739-3

Keywords

Navigation