Skip to main content
Top
Published in: European Journal of Nutrition 4/2015

01-06-2015 | Original Contribution

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

Authors: Ping Kang, Yulan Liu, Huiling Zhu, Shuang Li, Haifeng Shi, Feng Chen, Weibo Leng, Dinan Pi, Yongqing Hou, Dan Yi

Published in: European Journal of Nutrition | Issue 4/2015

Login to get access

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.
Literature
2.
go back to reference Fox CJ, Hammerman PS, Thompson CB (2005) Fuel feeds function: energy metabolism and the T-cell response Nat. Rev Immunol 5:844–852CrossRef Fox CJ, Hammerman PS, Thompson CB (2005) Fuel feeds function: energy metabolism and the T-cell response Nat. Rev Immunol 5:844–852CrossRef
3.
go back to reference 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 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
4.
go back to reference Alipour M, Omri A, Smith MG, Suntres ZE (2007) Prophylactic effect of liposomal N-acetylcysteine against LPS-induced liver injuries. J Endotoxin Res 13:297–304CrossRef Alipour M, Omri A, Smith MG, Suntres ZE (2007) Prophylactic effect of liposomal N-acetylcysteine against LPS-induced liver injuries. J Endotoxin Res 13:297–304CrossRef
5.
go back to reference 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 48:276–282CrossRef 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 48:276–282CrossRef
6.
go back to reference 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 10:1247–1255CrossRef 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 10:1247–1255CrossRef
7.
go back to reference Sambandam N, Lopaschuk GD (2003) AMP-activated protein kinase (AMPK) control of fatty acid and glucose metabolism in the ischemic heart. Prog Lipid Res 42:238–256CrossRef Sambandam N, Lopaschuk GD (2003) AMP-activated protein kinase (AMPK) control of fatty acid and glucose metabolism in the ischemic heart. Prog Lipid Res 42:238–256CrossRef
8.
go back to reference 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 579:2045–2050CrossRef 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 579:2045–2050CrossRef
9.
go back to reference Hardie DG (2007) AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol 8:774–785CrossRef Hardie DG (2007) AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol 8:774–785CrossRef
10.
go back to reference 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 87:384–390CrossRef 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 87:384–390CrossRef
11.
go back to reference 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 14:185–190CrossRef 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 14:185–190CrossRef
12.
go back to reference 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 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
13.
go back to reference 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 25:592–599CrossRef 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 25:592–599CrossRef
14.
go back to reference 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 25:456–462CrossRef 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 25:456–462CrossRef
15.
go back to reference 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 18:804–814CrossRef 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 18:804–814CrossRef
16.
go back to reference 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 19:504–515CrossRef 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 19:504–515CrossRef
17.
go back to reference NRC (1998) Nutrient requirements of Swine, 10th edn. National Academic Press, Washington NRC (1998) Nutrient requirements of Swine, 10th edn. National Academic Press, Washington
18.
go back to reference 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 106:357–363CrossRef 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 106:357–363CrossRef
19.
go back to reference 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 142:2017–2024CrossRef 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 142:2017–2024CrossRef
20.
go back to reference Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and 2−ΔΔCT method. Methods 25:402–408CrossRef Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and 2−ΔΔCT method. Methods 25:402–408CrossRef
21.
go back to reference Hardie DG, Hawley SA (2001) AMP-activated protein kinase: the energy charge hypothesis revisited. BioEssays 23:1112–1119CrossRef Hardie DG, Hawley SA (2001) AMP-activated protein kinase: the energy charge hypothesis revisited. BioEssays 23:1112–1119CrossRef
22.
go back to reference 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 176:227–233CrossRef 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 176:227–233CrossRef
23.
go back to reference 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 208:313–326CrossRef 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 208:313–326CrossRef
24.
go back to reference Currie PD, Sullivan DT (1994) Structure and expression of the gene encoding phosphofructokinase (PFK) in Drosophila melanogaster. J Biol Chem 269:24679–24687 Currie PD, Sullivan DT (1994) Structure and expression of the gene encoding phosphofructokinase (PFK) in Drosophila melanogaster. J Biol Chem 269:24679–24687
25.
go back to reference 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 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
26.
go back to reference Tessier JP, Thurner B, Jüngling E, Lückhoff A, Fischer Y (2003) Impairment of glucose metabolism in hearts from rats treated with endotoxin. Cardiovasc Res 60:119–130CrossRef Tessier JP, Thurner B, Jüngling E, Lückhoff A, Fischer Y (2003) Impairment of glucose metabolism in hearts from rats treated with endotoxin. Cardiovasc Res 60:119–130CrossRef
27.
go back to reference 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 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
28.
go back to reference 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 1830:5104–5111CrossRef 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 1830:5104–5111CrossRef
29.
go back to reference 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 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
30.
go back to reference 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 50:2055–2063CrossRef 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 50:2055–2063CrossRef
31.
go back to reference 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 574:73–83CrossRef 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 574:73–83CrossRef
32.
go back to reference 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–L504CrossRef 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–L504CrossRef
33.
go back to reference Hardie DG, Carling D, Carlson M (1998) The AMP-activated/SNF1 protein kinase subfamily: metabolic sensors of the eukaryotic cell? Annu Rev Biochem 67:821–855CrossRef Hardie DG, Carling D, Carlson M (1998) The AMP-activated/SNF1 protein kinase subfamily: metabolic sensors of the eukaryotic cell? Annu Rev Biochem 67:821–855CrossRef
34.
go back to reference 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 277:23977–23980CrossRef 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 277:23977–23980CrossRef
35.
go back to reference 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–E1286CrossRef 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–E1286CrossRef
36.
go back to reference Guarente L (2006) Sirtuins as potential targets for metabolic syndrome. Nature 444:868–874CrossRef Guarente L (2006) Sirtuins as potential targets for metabolic syndrome. Nature 444:868–874CrossRef
37.
go back to reference 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 127:1109–1122CrossRef 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 127:1109–1122CrossRef
38.
go back to reference Fernandez-Marcos PJ, Auwerx J (2011) Regulation of PGC-1a, a nodal regulator of mitochondrial biogenesis. Am J Clin Nutr 93:884S–890SCrossRef Fernandez-Marcos PJ, Auwerx J (2011) Regulation of PGC-1a, a nodal regulator of mitochondrial biogenesis. Am J Clin Nutr 93:884S–890SCrossRef
39.
go back to reference 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 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
Metadata
Title
The effect of aspartate on the energy metabolism in the liver of weanling pigs challenged with lipopolysaccharide
Authors
Ping Kang
Yulan Liu
Huiling Zhu
Shuang Li
Haifeng Shi
Feng Chen
Weibo Leng
Dinan Pi
Yongqing Hou
Dan Yi
Publication date
01-06-2015
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nutrition / Issue 4/2015
Print ISSN: 1436-6207
Electronic ISSN: 1436-6215
DOI
https://doi.org/10.1007/s00394-014-0739-3

Other articles of this Issue 4/2015

European Journal of Nutrition 4/2015 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.