Plasma levels of homocysteine and cysteine increased in pediatric NAFLD and strongly correlated with severity of liver damage

International Journal of Molecular Sciences

Volumn 15, Issue 11, 2014, Pages 21202-21214

  Pastore, Anna ^a   Alisi, Anna ^a   Di Giovamberardino, Gianna ^a   Crudele, Annalisa ^a   Ceccarelli, Sara ^a   Panera, Nadia ^a   Dionisi Vici, Carlo ^a   Nobili, Valerio ^a  

^a BAMBINO GESÙ CHILDREN S HOSPITAL   (Italy)

Author keywords

Cysteine; Cysteinylglycine; Glutathione; Homocysteine; Non alcoholic fatty liver disease (NAFLD); Non alcoholic steatohepatitis (NASH)

Indexed keywords

ALANINE AMINOTRANSFERASE; ASPARTATE AMINOTRANSFERASE; CYSTEINE; CYSTEINYLGLYCINE; GAMMA GLUTAMYLTRANSFERASE; GLUTATHIONE; HOMOCYSTEINE; TRIACYLGLYCEROL; DIPEPTIDE;

ARTICLE; CHILD; CONTROLLED STUDY; DISEASE SEVERITY; FEMALE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HISTOLOGY; HOMEOSTASIS MODEL ASSESSMENT; HUMAN; HUMAN TISSUE; INFLAMMATION; LIPID STORAGE; LIVER BIOPSY; LIVER FIBROSIS; LIVER INJURY; MAJOR CLINICAL STUDY; MALE; NONALCOHOLIC FATTY LIVER; OXIDATIVE STRESS; SCHOOL CHILD; BLOOD; LIVER; PATHOLOGY;

CHILD; CYSTEINE; DIPEPTIDES; GLUTATHIONE; HOMOCYSTEINE; HUMANS; LIVER; MALE; NON-ALCOHOLIC FATTY LIVER DISEASE;

EID: 84924239921     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms151121202     Document Type: Article

References (39)

1. Kleiner, D.E.; Brunt, E.M. Nonalcoholic fatty liver disease: Pathologic patterns and biopsy evaluation in clinical research. Semin. Liver Dis. 2012, 32, 3–13.
2. Lazo, M.; Clark, J.M. The epidemiology of nonalcoholic fatty liver disease: A global perspective. Semin. Liver Dis. 2008, 28, 339–350.
3. Nobili, V.; Svegliati-Baroni, G.; Alisi, A.; Miele, L.; Valenti, L.; Vajro, P. A 360-degree overview of paediatric NAFLD: Recent insights. J. Hepatol. 2013, 58, 1218–1229.
4. Tarantino, G.; Finelli, C. What about non-alcoholic fatty liver disease as a new criterion to define metabolic syndrome? World J. Gastroenterol. 2013, 19, 3375–3384.
5. Alisi, A.; Feldstein, A.E.; Villani, A.; Raponi, M.; Nobili, V. Pediatric nonalcoholic fatty liver disease: A multidisciplinary approach. Nat. Rev. Gastroenterol. Hepatol. 2012, 9, 152–161.
6. Gariani, K.; Philippe, J.; Jornayvaz, F.R. Non-alcoholic fatty liver disease and insulin resistance: From bench to bedside. Diabetes Metab. 2013, 39, 16–26.
7. Schuppan, D.; Schattenberg, J.M. Non-alcoholic steatohepatitis: Pathogenesis and novel therapeutic approaches. J. Gastroenterol. Hepatol. 2013, 28, 68–76.
8. Tarantino, G.; Savastano, S.; Colao, A. Hepatic steatosis, low-grade chronic inflammation and hormone/growth factor/adipokine imbalance. World J. Gastroenterol. 2010, 16, 4773–4783.
9. Rolo, A.P.; Teodoro, J.S.; Palmeira, C.M. Role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis. Free Radic. Biol. Med. 2012, 52, 59–69.
10. Takaki, A.; Kawai, D.; Yamamoto, K. Multiple hits, including oxidative stress, as pathogenesis and treatment target in non-alcoholic steatohepatitis (NASH). Int. J. Mol. Sci. 2013, 14, 20704–20728.
11. Finkelstein, J.D. Pathways and regulation of homocysteine metabolism in mammals. Semin. Thromb. Hemost. 2000, 26, 219–225.
12. Lu, S.C. Regulation of hepatic glutathione synthesis: Current concepts and controversies. FASEB J. 1999, 13, 1169–1183.
13. Al-Maskari, M.Y.; Waly, M.I.; Ali, A.; Al-Shuaibi, Y.S.; Ouhtit, A. Folate and vitamin B12 deficiency and hyperhomocysteinemia promote oxidative stress in adult type 2 diabetes. Nutrition 2012, 28, e23–e26.
14. Zhou, J.; Austin, R.C. Contributions of hyperhomocysteinemia to atherosclerosis: Causal relationship and potential mechanisms. BioFactors 2009, 35, 120–129.
15. Ozkan, Y.; Ozkan, E.; Simşek, B. Plasma total homocysteine and cysteine levels as cardiovascular risk factors in coronary heart disease. Int. J. Cardiol. 2002, 82, 269–277.
16. Pastore, A.; Noce, A.; di Giovamberardino, G.; de Stefano, A.; Callà, C.; Zenobi, R.; Dessì, M.; di Daniele, N. Homocysteine, cysteine, folate and vitamin B(12) status in type 2 diabetic patients with chronic kidney disease. J. Nephrol. 2014, doi:10.1007/s40620-014-0126-4.
17. Shimizu, H.; Kiyohara, Y.; Kato, I.; Kitazono, T.; Tanizaki, Y.; Kubo, M.; Ueno, H.; Ibayashi, S.; Fujishima, M.; Iida, M. Relationship between plasma glutathione levels and cardiovascular disease in a defined population: The Hisayama study. Stroke 2004, 35, 2072–2077.
18. Calabrese, V.; Cornelius, C.; Leso, V.; Trovato-Salinaro, A.; Ventimiglia, B.; Cavallaro, M.; Scuto, M.; Rizza, S.; Zanoli, L.; Neri, S. et al. Oxidative stress, glutathione status, sirtuin and cellular stress response in type 2 diabetes. Biochim. Biophys. Acta 2012, 1822, 729–736.
19. Mato, J.M.; Lu, S.C. Homocysteine, the bad thiol. Hepatology 2005, 41, 976–979.
20. Werstuck, G.H.; Lentz, S.R.; Dayal, S.; Hossain, G.S.; Sood, S.K.; Shi, Y.Y.; Zhou, J.; Maeda, N.; Krisans, S.K.; Malinow, M.R. et al. Homocysteine-induced endoplasmic reticulum stress causes dysregulation of the cholesterol and triglyceride biosynthetic pathways. J. Clin. Investig. 2001, 107, 1263–1273.
21. Obeid, R.; Herrmann, W. Homocysteine and lipids: S-Adenosyl methionine as a key intermediate. FEBS Lett. 2009, 583, 1215–1225.
22. Bravo, E.; Palleschi, S.; Aspichueta, P.; Buqué, X.; Rossi, B.; Cano, A.; Napolitano, M.; Ochoa, B.; Botham, K.M. High fat diet-induced non alcoholic fatty liver disease in rats is associated with hyperhomocysteinemia caused by down regulation of the transsulphuration pathway. Lipids Health Dis. 2011, 10, 60.
23. Aissa, A.F.; Tryndyak, V.; de Conti, A.; Melnyk, S.; Gomes, T.D.; Bianchi, M.L.; James, S.J.; Beland, F.A.; Antunes, L.M.; Pogribny, I.P. Effect of methionine-deficient and methionine-supplemented diets on the hepatic one-carbon and lipid metabolism in mice. Mol. Nutr. Food Res. 2014, 58, 1502–1512.
24. Gulsen, M.; Yesilova, Z.; Bagci, S.; Uygun, A.; Ozcan, A.; Ercin, C.N.; Erdil, A.; Sanisoglu, S.Y.; Cakir, E.; Ates, Y. et al. Elevated plasma homocysteine concentrations as a predictor of steatohepatitis in patients with non-alcoholic fatty liver disease. J. Gastroenterol. Hepatol. 2005, 20, 1448–1455.
25. Polyzos, S.A.; Kountouras, J.; Patsiaoura, K.; Katsiki, E.; Zafeiriadou, E.; Deretzi, G.; Zavos, C.; Gavalas, E.; Katsinelos, P.; Mane, V. et al. Serum homocysteine levels in patients with nonalcoholic fatty liver disease. Ann. Hepatol. 2012, 11, 68–76.
26. Kalhan, S.C.; Guo, L.; Edmison, J.; Dasarathy, S.; McCullough, A.J.; Hanson, R.W.; Milburn, M. Plasma metabolomic profile in nonalcoholic fatty liver disease. Metabolism 2011, 60, 404–413.
27. Nobili, V.; Pastore, A.; Gaeta, L.M.; Tozzi, G.; Comparcola, D.; Sartorelli, M.R.; Marcellini, M.; Bertini, E.; Piemonte, F. Glutathione metabolism and antioxidant enzymes in patients affected by nonalcoholic steatohepatitis. Clin. Chim. Acta 2005, 355, 105–111.
28. De Carvalho, S.C.; Muniz, M.T.; Siqueira, M.D.; Siqueira, E.R.; Gomes, A.V.; Silva, K.A.; Bezerra, L.C.; D’Almeida, V.; de Oliveira, C.P.; Pereira, L.M. Plasmatic higher levels of homocysteine in non-alcoholic fatty liver disease (NAFLD). Nutr. J. 2013, 12, 37.
29. Oliveira, C.P.; Stefano, J.T.; Cavaleiro, A.M.; Fortes, M.A.; Vieira, S.M.; Lima, V.M.; Santos, T.E.; Santos, V.N.; de Azevedo Salgado, A.L.; Parise, E.R. et al. Association of polymorphisms of glutamate-cystein ligase and microsomal triglyceride transfer protein genes in non-alcoholic fatty liver disease. J. Gastroenterol. Hepatol. 2010, 25, 357–361.
30. Koide, S.; Kugiyama, K.; Sugiyama, S.; Nakamura, S.; Fukushima, H.; Honda, O.; Yoshimura, M.; Ogawa, H. Association of polymorphism in glutamate-cysteine ligase catalytic subunit gene with coronary vasomotor dysfunction and myocardial infarction. J. Am. Coll. Cardiol. 2003, 41, 539–545.
31. Stipanuk, M.H.; Dominy, J.E., Jr.; Lee, J.I.; Coloso, R.M. Mammalian cysteine metabolism: New insights into regulation of cysteine metabolism. J. Nutr. 2006, 136, 1652S–1659S.
32. Oz, H.S.; Chen, T.S.; Neuman, M. Methionine deficiency and hepatic injury in a dietary steatohepatitis model. Dig. Dis. Sci. 2008, 53, 767–776.
33. Dahlhoff, C.; Worsch, S.; Sailer, M.; Hummel, B.A.; Fiamoncini, J.; Uebel, K.; Obeid, R.; Scherling, C.; Geisel, J.; Bader, B.L. et al. Methyl-donor supplementation in obese mice prevents the progression of NAFLD, activates AMPK and decreases acyl-carnitine levels. Mol. Metab. 2014, 3, 565–580.
34. Murphy, S.K.; Yang, H.; Moylan, C.A.; Pang, H.; Dellinger, A.; Abdelmalek, M.F.; Garrett, M.E.; Ashley-Koch, A.; Suzuki, A.; Tillmann, H.L. et al. Relationship between methylome and transcriptome in patients with nonalcoholic fatty liver disease. Gastroenterology 2013, 145, 1076–1087.
35. Torres, L.; Garcia-Trevijano, E.R.; Rodriguez, J.A.; Carretero, M.V.; Bustos, M.; Fernández, E.; Eguinoa, E.; Mato, J.M.; Avila, M.A. Induction of TIMP-1 expression in rat hepatic stellate cells and hepatocytes: A new role for homocysteine in liver fibrosis. Biochim. Biophys. Acta 1999, 1455, 12–22.
36. Matté, C.; Stefanello, F.M.; Mackedanz, V.; Pederzolli, C.D.; Lamers, M.L.; Dutra-Filho, C.S.; Dos Santos, M.F.; Wyse, A.T. Homocysteine induces oxidative stress, inflammatory infiltration, fibrosis and reduces glycogen/glycoprotein content in liver of rats. Int. J. Dev. Neurosci. 2009, 27, 337–344.
37. Woo, C.W.H.; Prathapasinghe, G.A.; Siow, Y.L.; O, K. Hyperhomocysteinemia induces liver injury in rat: Protective effect of folic acid supplementation. Biochim. Biophys. Acta 2006, 1762, 656–665.
38. Matthews, D.R.; Hosker, J.P.; Rudenski, A.S.; Naylor, B.A.; Treacher, D.F.; Turner, R.C. Homeostasis model assessment: Insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985, 28, 412–419.
39. Kleiner, D.E.; Brunt, E.M.; van Natta, M.; Behling, C.; Contos, M.J.; Cummings, O.W.; Ferrell, L.D.; Liu, Y.C.; Torbenson, M.S.; Unalp-Arida, A. et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005, 41, 1313–1321.