Skip to main content
Log in

High-salt diet affects amino acid metabolism in plasma and muscle of Dahl salt-sensitive rats

  • Original Article
  • Published:
Amino Acids Aims and scope Submit manuscript

Abstract

Genetic background and high-salt diet are considered key factors contributing to the development of hypertension and its associated metabolic disorders. Metabolomics is an emerging powerful tool to analyze the low-molecular weight metabolites in plasma and tissue. This study integrated metabolomics and correlation network analysis to investigate the metabolic profiles of plasma and muscle of Dahl salt-sensitive (SS) rats and SS.13BN rats (control) under normal and high-salt diet. The hub metabolites, which could play important roles in the metabolic changes, were identified by correlation network analysis. The results of the network analysis were further confirmed by pathway analysis and enzyme activity analysis. The results indicated a higher amino acid levels in both plasma and muscle of SS rats fed with high-salt diet. Alanine was found as a hub metabolite with the highest score of three centrality indices and also as the significant differential metabolite in plasma of SS rats after high-salt diet. Valine and lysine were found as hub metabolites and differential metabolites in muscle of SS rats after high-salt diet. Amino acid levels increased in both plasma and muscle of SS rats fed with a high salt diet. Moreover, alanine in plasma and valine and lysine in muscle as hub metabolites could play important roles in the response to high-salt diet.

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.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Ameta K, Gupta A, Kumar S, Sethi R, Kumar D, Mahdi AA (2017) Essential hypertension: a filtered serum based metabolomics study. Sci Rep 7(1):2153

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ananieva Elitsa A, Wilkinson Adam C (2017) Branched-chain amino acid metabolism in cancer. Curr Opin Clin Nutr Metab Care 21(1):64

    Article  PubMed Central  CAS  Google Scholar 

  • Arda E, Kara S, Sarac A, Pekcan O (1993) Effect of pH and sodium ions on intestinal uptake of lysine in rats. Indian J Exp Biol 31(6):529–532

    Google Scholar 

  • Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate—a practical and powerful approach to multiple testing. J R Stat Soc 57(1):289–300

    Google Scholar 

  • Brennan L, Shine A, Hewage C, Malthouse JP, Brindle KM, McClenaghan N, Flatt PR, Newsholme P (2002) A nuclear magnetic resonance-based demonstration of substantial oxidative l-alanine metabolism and l-alanine-enhanced glucose metabolism in a clonal pancreatic beta-cell line: metabolism of l-alanine is important to the regulation of insulin secretion. Diabetes 51(6):1714–1721

    Article  PubMed  CAS  Google Scholar 

  • Cahill GF (1970) Starvation in man. Clin Endocrinol Metab 5(2):397–415

    Article  Google Scholar 

  • Canfield LM, Chytil F (1978) Effect of low lysine diet on rat protein metabolism. J Nutr 108(8):1343–1347. https://doi.org/10.1093/jn/108.8.1343

    Article  PubMed  CAS  Google Scholar 

  • Chen J, Li X, Balnave D, Brake J (2005) The influence of dietary sodium chloride, arginine:lysine ratio, and methionine source on apparent ileal digestibility of arginine and lysine in acutely heat-stressed broilers. Poult Sci 84(2):294–297. https://doi.org/10.1093/ps/84.2.294

    Article  PubMed  CAS  Google Scholar 

  • Consoli A, Nurjhan N Jr, Reilly JJ, Bier DM, Gerich JE (1990) Mechanism of increased gluconeogenesis in noninsulin-dependent diabetes mellitus. Role of alterations in systemic, hepatic, and muscle lactate and alanine metabolism. J Clin Investig 86(6):2038–2045

    Article  PubMed  CAS  Google Scholar 

  • Deng J, Sitou K, Zhang Y, Ru Y, Hu Y (2016) Analyzing the Chinese landscape in anti-diabetic drug research: leading knowledge production institutions and thematic communities. Chin Med 11(1):13

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dettmer K, Aronov PA, Hammock BD (2007) Mass spectrometry-based metabolomics. Mass Spectrom Rev 26(1):51

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dixon G, Nolan J, Mcclenaghan N, Flatt PR, Newsholme P (2003) A comparative study of amino acid consumption by rat islet cells and the clonal beta-cell line BRIN-BD11—the functional significance of l-alanine. J Endocrinol 179(3):447–454

    Article  PubMed  CAS  Google Scholar 

  • Donovan DS, Solomon CG, Seely EW, Williams GH, Simonson DC (1993) Effect of sodium intake on insulin sensitivity. Am J Physiol 264(1):730–734

    Google Scholar 

  • Fujita T, Ando K (1984) Hemodynamic and endocrine changes associated with potassium supplementation in sodium-loaded hypertensives. Hypertension 6(2 Pt 1):184

    Article  PubMed  CAS  Google Scholar 

  • Gress TW, Nieto FJ, Shahar E, Wofford MR, Brancati FL (2000) Hypertension and antihypertensive therapy as risk factors for type 2 diabetes mellitus. Atherosclerosis risk in communities study. N Engl J Med 342(8):905–912

    Article  PubMed  CAS  Google Scholar 

  • Huang Y, Zhou M, Sun H, Wang Y (2011) Branched-chain amino acid metabolism in heart disease: an epiphenomenon or a real culprit? Cardiovasc Res 90(2):220–223. https://doi.org/10.1093/cvr/cvr070

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kekuda R, Prasad PD, Fei YJ, Torreszamorano V, Sinha S, Yangfeng TL, Leibach FH, Ganapathy V (1996) Cloning of the sodium-dependent, broad-scope, neutral amino acid transporter Bo from a human placental choriocarcinoma cell line. J Biol Chem 271(31):18657–18661

    Article  PubMed  CAS  Google Scholar 

  • Kreisberg RA (1972) Glucose-lactate inter-relations in man. N Engl J Med 287(3):132

    Article  PubMed  CAS  Google Scholar 

  • Li L, Jiang H, Qiu Y, Ching WK, Vassiliadis VS (2013) Discovery of metabolite biomarkers: flux analysis and reaction–reaction network approach. BMC Syst Biol 7(S2):1–7

    Google Scholar 

  • Loscalzo J (2011) Network medicine: a network-based approach to human disease. Nat Rev Genet 12(1):56

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lu Y, Wang Y, Ong CN, Subramaniam T, Choi HW, Yuan JM, Koh WP, Pan A (2016) Metabolic signatures and risk of type 2 diabetes in a Chinese population: an untargeted metabolomics study using both LC–MS and GC–MS. Diabetologia 59(11):1–11

    Article  CAS  Google Scholar 

  • Lynch CJ, Adams SH (2014) Branched-chain amino acids in metabolic signalling and insulin resistance. Nat Rev Endocrinol 10(12):723–736

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mahbub MH, Yamaguchi N, Takahashi H, Hase R, Ishimaru Y, Sunagawa H, Amano H, Kobayashi-Miura M, Kanda H, Fujita Y, Yamamoto H, Yamamoto M, Kikuchi S, Ikeda A, Kageyama N, Nakamura M, Tanabe T (2017) Association of plasma free amino acids with hyperuricemia in relation to diabetes mellitus, dyslipidemia, hypertension and metabolic syndrome. Sci Rep 7(1):17616. https://doi.org/10.1038/s41598-017-17710-6

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Menni C, Fauman E, Erte I, Perry JR, Kastenmuller G, Shin SY, Petersen AK, Hyde C, Psatha M, Ward KJ, Yuan W, Milburn M, Palmer CN, Frayling TM, Trimmer J, Bell JT, Gieger C, Mohney RP, Brosnan MJ, Suhre K, Soranzo N, Spector TD (2013) Biomarkers for type 2 diabetes and impaired fasting glucose using a nontargeted metabolomics approach. Diabetes 62(12):4270–4276. https://doi.org/10.2337/db13-0570

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Michailidis G (2012) Statistical challenges in biological networks. J Comput Graph Stat 21(4):840–855

    Article  Google Scholar 

  • Morales PA, Mitchell BD, Valdez RA, Hazuda HP, Stern MP, Haffner SM (1993) Incidence of NIDDM and impaired glucose tolerance in hypertensive subjects: the san antonio heart study. Diabetes 42(1):154

    Article  PubMed  CAS  Google Scholar 

  • Mu C, Yang Y, Luo Z, Zhu W (2015) Metabolomic analysis reveals distinct profiles in the plasma and urine of rats fed a high-protein diet. Amino Acids 47(6):1225–1238. https://doi.org/10.1007/s00726-015-1949-6

    Article  PubMed  CAS  Google Scholar 

  • Nikolic SB, Sharman JE, Adams MJ, Edwards LM (2014) Metabolomics in hypertension. J Hypertens 32(6):1159–1169

    Article  PubMed  CAS  Google Scholar 

  • Patience JF (1990) A review of the role of acid-base balance in amino acid nutrition. J Anim Sci 68(2):398–408

    Article  PubMed  CAS  Google Scholar 

  • Pinho MJ, Pinto V, Serrão MP, Jose PA, Soares-Da-Silva P (2007) Underexpression of the Na+ -dependent neutral amino acid transporter ASCT2 in the spontaneously hypertensive rat kidney. Am J Physiol Regul Integr Comp Physiol 293(1):R538

    Article  PubMed  CAS  Google Scholar 

  • Roberts LD, Koulman A, Griffin JL (2014) Towards metabolic biomarkers of insulin resistance and type 2 diabetes: progress from the metabolome. Lancet Diabetes Endocrinol 2(1):65–75

    Article  PubMed  CAS  Google Scholar 

  • Sato T, Ito Y, Nagasawa T (2013) Regulation of skeletal muscle protein degradation and synthesis by oral administration of lysine in rats. J Nutr Sci Vitaminol 59(5):412

    Article  PubMed  CAS  Google Scholar 

  • Shah SH, Crosslin DR, Haynes CS, Nelson S, Turer CB, Stevens RD, Muehlbauer MJ, Wenner BR, Bain JR, Laferrère B (2012) Branched-chain amino acid levels are associated with improvement in insulin resistance with weight loss. Diabetologia 55(2):321

    Article  PubMed  CAS  Google Scholar 

  • Stöckli J, Fisherwellman KH, Chaudhuri R, Zeng XY, Fazakerley DJ, Meoli CC, Thomas KC, Hoffman NJ, Mangiafico SP, Xirouchaki CE (2017) Metabolomic analysis of insulin resistance across different mouse strains and diets. J Biol Chem 292(47):19135–19145

    Article  PubMed  Google Scholar 

  • Suliman ME, Qureshi AR, Stenvinkel P, Pecoitsfilho R, Bárány P, Heimbürger O, Anderstam B, Rodríguez AE, Divino Filho JC, Alvestrand A (2005) Inflammation contributes to low plasma amino acid concentrations in patients with chronic kidney disease. Am J Clin Nutr 82(2):342–349

    Article  PubMed  CAS  Google Scholar 

  • Tanphaichitr V, Broquist HP (1973) Role of lysine and N-trimethyllysine in carnitine biosynthesis. II. Studies in the rat. J Biol Chem 248(6):2176–2181

    PubMed  CAS  Google Scholar 

  • Wang X, Yang B, Sun H, Zhang A (2012) Pattern recognition approaches and computational systems tools for ultra performance liquid chromatography–mass spectrometry-based comprehensive metabolomic profiling and pathways analysis of biological data sets. Anal Chem 84(1):428–439

    Article  PubMed  CAS  Google Scholar 

  • Wang L, Zheng L, Luo R, Zhao X, Han Z, Wang Y, Yang Y (2014) A 1H NMR-based metabonomic investigation of time-dependent metabolic trajectories in high salt-induced hypertension rat model. RSC Adv 5(1):281–290

    Article  CAS  Google Scholar 

  • Wang L, Hou E, Wang L, Wang Y, Yang L, Zheng X, Xie G, Sun Q, Liang M, Tian Z (2015) Reconstruction and analysis of correlation networks based on GC–MS metabolomics data for young hypertensive men. Anal Chim Acta 854:95

    Article  PubMed  CAS  Google Scholar 

  • Wang Z, Sun Q, Sun N, Liang M, Tian Z (2017) Mitochondrial dysfunction and altered renal metabolism in Dahl salt-sensitive rats. Kidney Blood Press Res 42(3):587–597

    Article  PubMed  CAS  Google Scholar 

  • Yang RY, Wang SM, Sun L, Liu JM, Li HX, Sui XF, Wang M, Xiu HL, Wang S, He Q (2015) Association of branched-chain amino acids with coronary artery disease: a matched-pair case–control study. Nutr Metab Cardiovasc Dis 25(10):937

    Article  PubMed  CAS  Google Scholar 

  • Zhang AD, Dai SX (2013) Huang JF (2013) Reconstruction and analysis of human kidney-specific metabolic network based on omics data. BioMed Res Int 1:187509

    Google Scholar 

  • Zhang M, Zhu C, Jacomy A, Lu L, Jegga A (2011) The orphan disease networks. Am J Hum Genet 88(6):755

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Acknowledgements

The authors are grateful for the support provided by National Natural Science Foundation of China (NSFC) (Grant nos. 81570655, 81770728, 51703178).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Dan Gao or Zhongmin Tian.

Ethics declarations

Conflict of interest

All the authors declare that they have no conflict of interest.

Animal rights

All experiments were performed according to the guidelines of the National Institutes of Health and the institutional rules for the use and care of laboratory animals at Xi’an Jiaotong University.

Additional information

Handling Editor: S. Gross.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 988 kb)

Supplementary material 2 (DOCX 21 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lin, W., Liu, Z., Zheng, X. et al. High-salt diet affects amino acid metabolism in plasma and muscle of Dahl salt-sensitive rats. Amino Acids 50, 1407–1414 (2018). https://doi.org/10.1007/s00726-018-2615-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00726-018-2615-6

Keywords

Navigation