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Branched Chain Amino Acids in Heart Failure

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Branched Chain Amino Acids in Clinical Nutrition

Part of the book series: Nutrition and Health ((NH))

Abstract

Branched-Chain Amino Acids (BCAA) are essential amino acids for protein synthesis and also serve as critical signaling molecules for cellular growth and metabolic regulations. The homeostasis of BCAA is regulated by food uptake and intrinsic catabolic activities. Genetic defects in BCAA catabolic pathways can cause cardiomyopathies and suppressed BCAA catabolic activities are observed in common forms of human heart diseases. However, the cellular and molecular mechanisms of BCAA function and its misregulation under pathological stress in heart diseases remain to be explored. Nevertheless, BCAA catabolic regulation is potential diagnosis and therapeutic target for heart failure.

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References

  1. Baquet A, Lavoinne A, Hue L. Comparison of the effects of various amino acids on glycogen synthesis, lipogenesis and ketogenesis in isolated rat hepatocytes. Biochem J. 1991;273(Pt 1):57–62. PMC:1149878.

    CAS  PubMed Central  PubMed  Google Scholar 

  2. Harper AE, Miller RH, Block KP. Branched-chain amino acid metabolism. Annu Rev Nutr. 1984;4:409–54.

    Article  CAS  PubMed  Google Scholar 

  3. Potier M, Darcel N, Tome D. Protein, amino acids and the control of food intake. Curr Opin Clin Nutr Metab Care. 2009;12(1):54–8.

    Article  CAS  PubMed  Google Scholar 

  4. Marc Rhoads J, Wu G. Glutamine, arginine, and leucine signaling in the intestine. Amino Acids. 2009;37(1):111–22.

    Article  CAS  PubMed  Google Scholar 

  5. Avruch J, Long X, Ortiz-Vega S, Rapley J, Papageorgiou A, Dai N. Amino acid regulation of TOR complex 1. Am J Physiol Endocrinol Metab. 2009;296(4):E592–602. PMC:2670622.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Meijer AJ. Amino acid regulation of autophagosome formation. Methods Mol Biol. 2008;445:89–109.

    Article  CAS  PubMed  Google Scholar 

  7. Vary TC, Lynch CJ. Nutrient signaling components controlling protein synthesis in striated muscle. J Nutr. 2007;137(8):1835–43.

    CAS  PubMed  Google Scholar 

  8. Chotechuang N, Azzout-Marniche D, Bos C, Chaumontet C, Gausseres N, Steiler T, Gaudichon C, Tome D. mTOR, AMPK, and GCN2 coordinate the adaptation of hepatic energy metabolic pathways in response to protein intake in the rat. Am J Physiol Endocrinol Metab. 2009;297(6):E1313–23.

    Article  CAS  PubMed  Google Scholar 

  9. Harris RA, Joshi M, Jeoung NH. Mechanisms responsible for regulation of branched-chain amino acid catabolism. Biochem Biophys Res Commun. 2004;313(2):391–6.

    Article  CAS  PubMed  Google Scholar 

  10. Hutson SM, Sweatt AJ, LaNoue KF. Branched-chain amino acid metabolism: implications for establishing safe intakes. J Nutr. 2005;135(6):1557S–64.

    CAS  PubMed  Google Scholar 

  11. Tso S-C, Qi X, Gui W-J, Chuang JL, Morlock LK, Wallace AL, Ahmed K, Laxman S, Campeau PM, Lee BH, Hutson SM, Tu BP, Williams NS, Tambar UK, Wynn RM, Chuang DT. Structure-based design and mechanisms of allosteric inhibitors for mitochondrial branched-chain α-ketoacid dehydrogenase kinase. Proc Natl Acad Sci. 2013;110(24):9728–33.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Herman MA, She P, Peroni OD, Lynch CJ, Kahn BB. Adipose tissue branched chain amino acid (BCAA) metabolism modulates circulating BCAA levels. J Biol Chem. 2010;285(15):11348–56.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Joshi MA, Jeoung NH, Obayashi M, Hattab EM, Brocken EG, Liechty EA, Kubek MJ, Vattem KM, Wek RC, Harris RA. Impaired growth and neurological abnormalities in branched-chain α-keto acid dehydrogenase kinase-deficient mice. Biochem J. 2006;400(1):153–62.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Fuller TF, Ghazalpour A, Aten JE, Drake TA, Lusis AJ, Horvath S. Weighted gene coexpression network analysis strategies applied to mouse weight. Mamm Genome. 2007;18(6–7):463–72.

    Article  PubMed Central  PubMed  Google Scholar 

  15. Zhou M, Lu G, Gao C, Wang Y, Sun H. Tissue-specific and nutrient regulation of the branched-chain α-keto acid dehydrogenase phosphatase, protein phosphatase 2Cm (PP2Cm). J Biol Chem. 2012;287(28):23397–406.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Nishimura J, Masaki T, Arakawa M, Seike M, Yoshimatsu H. Isoleucine prevents the accumulation of tissue triglycerides and upregulates the expression of PPARalpha and uncoupling protein in diet-induced obese mice. J Nutr. 2010;140(3):496–500.

    Article  CAS  PubMed  Google Scholar 

  17. Proud CG. Regulation of mammalian translation factors by nutrients. Eur J Biochem. 2002;269(22):5338–49.

    Article  CAS  PubMed  Google Scholar 

  18. Zhang D, Contu R, Latronico MVG, Zhang J, Rizzi R, Catalucci D, Miyamoto S, Huang K, Ceci M, Gu Y, Dalton ND, Peterson KL, Guan K-L, Brown JH, Chen J, Sonenberg N, Condorelli G. MTORC1 regulates cardiac function and myocyte survival through 4E-BP1 inhibition in mice. J Clin Invest. 2010;120(8):2805–16.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Katta A, Kundla S, Kakarla SK, Wu M, Fannin J, Paturi S, Liu H, Addagarla HS, Blough ER. Impaired overload-induced hypertrophy is associated with diminished mTOR signaling in insulin-resistant skeletal muscle of the obese Zucker rat. Am J Physiol Regul Integr Comp Physiol. 2010;299(6):R1666–75.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Meijer AJ, Dubbelhuis PF. Amino acid signalling and the integration of metabolism. Biochem Biophys Res Commun. 2004;313(2):397–403.

    Article  CAS  PubMed  Google Scholar 

  21. Newgard CB, An J, Bain JR, Muehlbauer MJ, Stevens RD, Lien LF, Haqq AM, Shah SH, Arlotto M, Slentz CA, Rochon J, Gallup D, Ilkayeva O, Wenner BR, Yancy Jr WS, Eisenson H, Musante G, Surwit RS, Millington DS, Butler MD, Svetkey LP. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab. 2009;9(4):311–26.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Xiao F, Huang Z, Li H, Yu J, Wang C, Chen S, Meng Q, Cheng Y, Gao X, Li J, Liu Y, Guo F. Leucine deprivation increases hepatic insulin sensitivity Via GCN2/mTOR/S6K1 and AMPK pathways. Diabetes. 2011;60(3):746–56.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Nicklin P, Bergman P, Zhang B, Triantafellow E, Wang H, Nyfeler B, Yang H, Hild M, Kung C, Wilson C, Myer VE, MacKeigan JP, Porter JA, Wang YK, Cantley LC, Finan PM, Murphy LO. Bidirectional transport of amino acids regulates mTOR and autophagy. Cell. 2009;136(3):521–34.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Nishida K, Kyoi S, Yamaguchi O, Sadoshima J, Otsu K. The role of autophagy in the heart. Cell Death Differ. 2009;16(1):31–8.

    Article  CAS  PubMed  Google Scholar 

  25. D’Antona G, Ragni M, Cardile A, Tedesco L, Dossena M, Bruttini F, Caliaro F, Corsetti G, Bottinelli R, Carruba MO, Valerio A, Nisoli E. Branched-chain amino acid supplementation promotes survival and supports cardiac and skeletal muscle mitochondrial biogenesis in middle-aged mice. Cell Metab. 2010;12(4):362–72.

    Article  PubMed  Google Scholar 

  26. Arn P, Funanage VL. 3-methylglutaconic aciduria disorders: the clinical spectrum increases. J Pediatr Hematol Oncol. 2006;28(2):62–3.

    Article  PubMed  Google Scholar 

  27. Bowles KR, Bowles NE. Genetics of inherited cardiomyopathies. Expert Rev Cardiovasc Ther. 2004;2(5):683–97.

    Article  CAS  PubMed  Google Scholar 

  28. Draaisma JM, van Kesteren IC, Daniels O, Sengers RC. Dilated cardiomyopathy with 3-methylglutaconic aciduria. Pediatr Cardiol. 1994;15(2):89–90.

    Article  CAS  PubMed  Google Scholar 

  29. Romano S, Valayannopoulos V, Touati G, Jais JP, Rabier D, de Keyzer Y, Bonnet D, de Lonlay P. Cardiomyopathies in propionic aciduria are reversible after liver transplantation. J Pediatr. 2010;156(1):128–34.

    Article  PubMed  Google Scholar 

  30. Lu G, Sun H, She P, Youn JY, Warburton S, Ping P, Vondriska TM, Cai H, Lynch CJ, Wang Y. Protein phosphatase 2Cm is a critical regulator of branched-chain amino acid catabolism in mice and cultured cells. J Clin Invest. 2009;119(6):1678–87.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Lu G, Ren S, Korge P, Choi J, Dong Y, Weiss J, Koehler C, Chen JN, Wang Y. A novel mitochondrial matrix serine/threonine protein phosphatase regulates the mitochondria permeability transition pore and is essential for cellular survival and development. Genes Dev. 2007;21(7):784–96.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Sun H, Lu G, Ren S, Chen J, Wang Y. Catabolism of branched-chain amino acids in heart failure: insights from genetic models. Pediatr Cardiol. 2011;32(3):305–10.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Shah SH, Bain JR, Muehlbauer MJ, Stevens RD, Crosslin DR, Haynes C, Dungan J, Newby LK, Hauser ER, Ginsburg GS, Newgard CB, Kraus WE. Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events/CLINICAL PERSPECTIVE. Circ Cardiovasc Genet. 2010;3(2):207–14.

    Article  CAS  PubMed  Google Scholar 

  34. Kato T, Niizuma S, Inuzuka Y, Kawashima T, Okuda J, Tamaki Y, Iwanaga Y, Narazaki M, Matsuda T, Soga T, Kita T, Kimura T, Shioi T. Analysis of metabolic remodeling in compensated left ventricular hypertrophy and heart failure. Circulation: Heart Failure; 2010.

    Google Scholar 

  35. Héliès-Toussaint C, Moinard C, Rasmusen C, Tabbi-Anneni I, Cynober L, Grynberg A. Aortic banding in rat as a model to investigate malnutrition associated with heart failure. Am J Physiol Regul Integr Comp Physiol. 2005;288(5):R1325–31.

    Article  PubMed  Google Scholar 

  36. Bing RJ, Siegel A, Vitale A, Balboni F, Sparks E, Taeschler M, Klapper M, Edwards S. Metabolic studies on the human heart in vivo. I Studies on carbohydrate metabolism of the human heart. Am J Med. 1953;15(3):284–96.

    Article  CAS  PubMed  Google Scholar 

  37. Ingwall JS. Energy metabolism in heart failure and remodelling. Cardiovasc Res. 2009;81(3):412–9. PMC:2639129.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Guertl B, Noehammer C, Hoefler G. Metabolic cardiomyopathies. Int J Exp Pathol. 2000;81(6):349–72.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Lee J-H, Gao C, Peng G, Greer C, Ren S, Wang Y, Xiao X. Analysis of transcriptome complexity through RNA sequencing in normal and failing murine hearts/novelty and significance. Circ Res. 2011;109(12):1332–41.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Mochel F, Charles P, Seguin FO, Barritault J, Coussieu C, Perin L, Le Bouc Y, Gervais C, Carcelain G, Vassault A, Feingold J, Rabier D, Durr A. Early energy deficit in Huntington disease: identification of a plasma biomarker traceable during disease progression. PLoS One. 2007;2(7):e647.

    Article  PubMed Central  PubMed  Google Scholar 

  41. Wang TJ, Larson MG, Vasan RS, Cheng S, Rhee EP, McCabe E, Lewis GD, Fox CS, Jacques PF, Fernandez C, O’Donnell CJ, Carr SA, Mootha VK, Florez JC, Souza A, Melander O, Clish CB, Gerszten RE. Metabolite profiles and the risk of developing diabetes. Nat Med. 2011;17(4):448–53.

    Article  PubMed Central  PubMed  Google Scholar 

  42. Yudkoff M, Daikhin Y, Nissim I, Horyn O, Luhovyy B, Lazarow A. Brain amino acid requirements and toxicity: the example of leucine. J Nutr. 2005;135(6 Suppl):1531S–8.

    CAS  PubMed  Google Scholar 

  43. Saha AK, Xu XJ, Lawson E, Deoliveira R, Brandon AE, Kraegen EW, Ruderman NB. Downregulation of AMPK accompanies leucine- and glucose-induced increases in protein synthesis and insulin resistance in rat skeletal muscle. Diabetes. 2010;59(10):2426–34.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. Kim S, Buel G, Blenis J. Nutrient regulation of the mTOR Complex 1 signaling pathway. Mol Cells. 2013;1–11.

    Google Scholar 

  45. Hill JA. Autophagy in cardiac plasticity and disease. Pediatr Cardiol. 2011;32(3):282–9.

    Article  PubMed Central  PubMed  Google Scholar 

  46. Aviv Y, Shaw J, Gang H, Kirshenbaum LA. Regulation of autophagy in the heart: “You Only Live Twice”. Antioxid Redox Signal. 2011;14(11):2245–50.

    Article  CAS  PubMed  Google Scholar 

  47. Gustafsson AB, Gottlieb RA. Autophagy in ischemic heart disease. Circ Res. 2009;104(2):150–8. PMC:2765251.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. de Keyzer Y, Valayannopoulos V, Benoist JF, Batteux F, Lacaille F, Hubert L, Chretien D, Chadefeaux-Vekemans B, Niaudet P, Touati G, Munnich A, de Lonlay P. Multiple OXPHOS deficiency in the liver, kidney, heart, and skeletal muscle of patients with methylmalonic aciduria and propionic aciduria. Pediatr Res. 2009;66(1):91–5.

    Article  PubMed  Google Scholar 

  49. Shestopalov A, Kristal B. Branched chain keto-acids exert biphasic effects on α-ketoglutarate-stimulated respiration in intact rat liver mitochondria. Neurochem Res. 2007;32(4):947–51.

    Article  CAS  PubMed  Google Scholar 

  50. Sgaravatti AM, Rosa RB, Schuck PF, Ribeiro CAJ, Wannmacher CMD, Wyse ATS, Dutra-Filho CS, Wajner M. Inhibition of brain energy metabolism by the [alpha]-keto acids accumulating in maple syrup urine disease. Biochim Biophys Acta. 2003;1639(3):232–8.

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Division of Molecular Medicine, Departments of Anesthesiology, Physiology and Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Haipeng Sun Ph.D.

  2. Division of Molecular Medicine, Departments of Anesthesiology, Physiology and Medicine, Cardiovascular Research Laboratory, Molecular Biology Institute, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

    Yibin Wang Ph.D.

Authors
  1. Haipeng Sun Ph.D.
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  2. Yibin Wang Ph.D.
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Corresponding author

Correspondence to Haipeng Sun Ph.D. .

Editor information

Editors and Affiliations

  1. Intensive Care, Barnet and Chase Farm Hospitals, Royal Free London NHS Foundation Trust, London, United Kingdom

    Rajkumar Rajendram

  2. Diabetes and Nutritional Sciences, Kings College London, London, United Kingdom

    Victor R. Preedy

  3. Department of Biomedical Sciences, University of Westminster, London, United Kingdom

    Vinood B. Patel

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Sun, H., Wang, Y. (2015). Branched Chain Amino Acids in Heart Failure. In: Rajendram, R., Preedy, V., Patel, V. (eds) Branched Chain Amino Acids in Clinical Nutrition. Nutrition and Health. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1914-7_6

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  • DOI: https://doi.org/10.1007/978-1-4939-1914-7_6

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  • Publisher Name: Humana Press, New York, NY

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  • Online ISBN: 978-1-4939-1914-7

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