Oxidative Stress in Metabolic Syndrome: Experimental Model of Biomarkers

  • María del Carmen Baez
  • Mariana Tarán
  • Mónica Moya
  • María de la Paz Scribano Parada


Metabolic syndrome (MS) is characterized by the convergence of several risk factors at the same time in which each individual contributes to cardiovascular risk. Although the factors that establish the relationship between metabolic alterations and vascular changes that predispose to cardiovascular events are not fully understood, it is likely that endothelial dysfunction has decisive importance in this regard. We implemented the use of fibrinogen, nitric oxide, adiponectin, and superoxide dismutase, to evaluate the implication of these phenomena in mitochondrial function and morphology in a MS model. It was demonstrated that the sustained oxidative stress situation induces histological alterations at the aortic level. This pathological and oxidative state leads to a mitochondrial dysfunction with repercussion in the morphology of this organelle.

Due to the intimate link to insulin resistance (IR), obesity, and MS, the importance of studying the implication of the inflammatory phenomenon and associated oxidative stress is understood, in order to establish the probable physiopathogenic mechanisms with the aim of generating strategies that prevent the incidence and prevalence of this pathology, given that it has huge consequences in health system. For this it is necessary to identify the determinants of the disease in order to implement preventive measures for control and monitoring as well as to study therapeutic strategies that can be implemented to reduce the incidence of this multisyndromic pathology.


Metabolic syndrome Oxidative stress Mitochondria 


  1. 1.
    Grundy SM (2007) Metabolic syndrome: a multiplex cardiovascular risk factor. J Clin Endocrinol Metab 92:399–404PubMedCrossRefGoogle Scholar
  2. 2.
    Grandl G, Wolfrum C (2018) Hemostasis, endothelial stress, inflammation, and the metabolic syndrome. Semin Immunopathol 40(2):215–224. Scholar
  3. 3.
    Gómez M, Manuel A, Patino Alonso MP et al (2013) Confirmatory factor analysis to assess the measure of adiposity that best fits the diagnosis of metabolic syndrome and relationship to physical activity in adults. European Journal of Nutrition, relationship to physical activity in adults. Eur J Nutr 52(5):1451–1459CrossRefGoogle Scholar
  4. 4.
    Palomo IG, Gutiérrez CL, Alarcón ML et al (2009) Increased concentration of plasminogen activator inhibitor-1 and fibrinogen in individuals with metabolic syndrome. Mol Med Rep 2(2):253–257PubMedGoogle Scholar
  5. 5.
    Palomo IG, Moore-Carrasco R, Alarcon M et al (2010) Pathophysiology of the proatherothrombotic state in the metabolic syndrome. Front Biosci 2:194–208Google Scholar
  6. 6.
    Fernández-García JC, Cardona F, Tinahones FJ (2013) Inflammation, oxidative stress and metabolic syndrome: dietary modulation. Curr Vasc Pharmacol 11(6):906–919PubMedCrossRefGoogle Scholar
  7. 7.
    Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA et al (2009) Harmonizing the metabolic syndrome: a joint interim statement of the international Diabetes Federation Task force on epidemiology and prevention; National Heart, Lung, and Blood Institute; American heart Association; World heart Federation; International Atherosclerosis Society; and International Association for the study of obesity. Circulation 20:1640–1645CrossRefGoogle Scholar
  8. 8.
    Ghezzi P, Bonetto V, Fratelli M (2013) Thiol–disulfide balance: from the concept of oxidative stress to that of redox regulation. Antioxid Redox Signal 7(7–8):964–972Google Scholar
  9. 9.
    Nikolopoulou A, Kadoglou NP (2012) Obesity and metabolic syndrome as related to cardiovascular disease. Expert Rev Cardiovasc Ther 10(7):933–939PubMedCrossRefGoogle Scholar
  10. 10.
    Krintus M, Kozinski M, Kubica J, Sypniewska G (2014) Critical appraisal of inflammatory markers in cardiovascular risk stratification. Crit Rev Clin Lab Sci 51:263–279. Scholar
  11. 11.
    Stoner L, Lucero AA, Palmer BR, Jones LM, Young JM, Faulkner J (2013) Inflammatory biomarkers for predicting cardiovascular disease. Clin Biochem 46(15):1353–1371PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Lowe F (2014) Biomarkers of oxidative stress. Syst Biol Free Radicals Antioxid:65–87Google Scholar
  13. 13.
    Packard RR, Libby P (2008) Inflammation in atherosclerosis: from vascular biology to biomarker discovery and risk prediction. Clin Chem 54(1):24–38PubMedCrossRefGoogle Scholar
  14. 14.
    Monteiro R, Azevedo I (2010) Chronic inflammation in obesity and the metabolic syndrome. Mediat Inflamm 2010:1–10. Article ID 289645. Scholar
  15. 15.
    Vazzana N, Santilli F, Sestili S, Cuccurullo C, Davi G (2011) Determinants of increased cardiovascular disease in obesity and metabolic syndrome. Curr Med Chem 18(34):5267–5280PubMedCrossRefGoogle Scholar
  16. 16.
    Esposito K, Ciotola M, Giugliano D et al (2006) Oxidative stress in the metabolic syndrome. J Endocrinol Investig 29(9):791–795CrossRefGoogle Scholar
  17. 17.
    Sandra S, Arango V (2012) Biomarkers for the evaluation of human health risks. Rev Fac Nac Salud Pública 30(1):75–82Google Scholar
  18. 18.
    Roos CJ, Quax PH, Jukema JW (2012) Cardiovascular metabolic syndrome: mediators involved in the pathophysiology from obesity to coronary heart disease. Biomark Med 6(1):35–52PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Duarte MJ, Espinosa López RF, Diaz MS, Sánchez Rojas G (2008) Nitric oxide: metabolism and clinical implications. Med Int 24(6):397–406Google Scholar
  20. 20.
    Baez MC, Tarán M, Scribano MP, Balceda A, Buonanotte C, Blencio S, Fonseca S, Moya M (2017) Inflammatory and oxidative stress markers as indicator of atherogenesis in rats: antioxidants as preventive pharmacological methods. Anti-Inflammatory Anti-Allergy Agents Med Chem 16:1–7Google Scholar
  21. 21.
    Carrillo Calvillo J, Bear Sandoval IR (2004) Biomarkers, inflammation, oxidative stress, lipids and atherothrombosis atherosclerosis: an inflammatory process. Arch Cardiol Mex 74(2):S379–S384Google Scholar
  22. 22.
    Bonomini F, Tengattini S, Fabiano A, Bianchi R, Rezzani R (2008) Atherosclerosis and oxidative stress. Histol Histopathol 23(3):381–390PubMedGoogle Scholar
  23. 23.
    Zweier JL, Li H, Samouilov A, Liu X (2010) Mechanisms of nitrite reduction to nitric oxide in the heart and vessel wall. Nitric Oxide 22(2):83–90PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Gleissner CA, Leitinger N, Ley K (2007) Effects of native and modifi ed low-density lipoproteins on monocyte recruitment in atherosclerosis. Hypertension 50(2):276–283PubMedCrossRefGoogle Scholar
  25. 25.
    Thomas SR, Witting PK, Drummond GR (2008) Redox control of endothelial function and dysfunction: molecular mechanisms and therapeutic opportunities. Antioxid Redox Signal 10(10):1713–1766PubMedCrossRefGoogle Scholar
  26. 26.
    Victor VM, Rocha M, Solá E, Bañuls C, Garcia-Malpartida K, Hernández-Mijares A (2009) Oxidative stress, endothelial dysfunction and atherosclerosis. Curr Pharm Des 15(26):2988–3002PubMedCrossRefGoogle Scholar
  27. 27.
    Brand MD (2016) Mitochondrial generation of superoxide and hydrogen peroxide as the source of mitochondrial redox signaling. Free Radic Biol Med 100:14–31PubMedCrossRefGoogle Scholar
  28. 28.
    Battes LC, Cheng JM, Oemrawsingh RM, Boersma E, Garcia-Garcia HM, de Boer SP et al (2014) Circulating cytokines in relation to the extent and composition of coronary atherosclerosis: results from the ATHEROREMO-IVUS study. Atherosclerosis 236(1):18–24PubMedCrossRefGoogle Scholar
  29. 29.
    Abello N et al (2009) Protein tyrosine nitration: selectivity, physicochemical and biological consequences, denitration, and proteomics methods for the identification of tyrosine-nitrated proteins. J Proteome Res 8(7):3222–3238PubMedCrossRefGoogle Scholar
  30. 30.
    Surmeli NB, Litterman NK, Miller AF, Groves JT (2010) Peroxynitrite mediates active site tyrosine nitration in manganese superoxide dismutase. Evidence of a role for the carbonate radical anion. J Am Chem Soc 132(48):17174–17185PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Li LF, Li J (2007) Link between oxidative stress and insulin resistance. Chin Med Sci J 22(4):254–259PubMedGoogle Scholar
  32. 32.
    Puddu P, Puddu G, Cravero E, De Pascalis S, Muscari A (2009) The emerging role of cardiovascular risk factor-induced mitochondrial dysfunction in atherogenesis. J Biomed Sci 16:112. Scholar
  33. 33.
    Karbach S, Wenzel P, Waisman A, Münzel T, Daiber A (2014) eNOS uncoupling in cardiovascular diseases – the role of oxidative stress and inflammation. Curr Pharm Des 20(22):3579–3594PubMedCrossRefGoogle Scholar
  34. 34.
    Ježek P, Dlasková A, Plecitá-Hlavatá L (2012) Redox homeostasis in pancreatic β cells. Oxidative Med Cell Longev 2012:932838. Scholar
  35. 35.
    Bakhtiari A, Hajian-Tilaki K, Omidvar S, Nasiri Amiri F (2017) Association of lipid peroxidation and antioxidant status with metabolic syndrome in Iranian healthy elderly women. Biomed Rep 7(4):331–336PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Kamath S, Lip GY (2003) Fibrinogen: biochemistry, epidemiology and determinants. QJM 96:711–729PubMedCrossRefGoogle Scholar
  37. 37.
    Moya M, Scribano MP, Baez M (2017) Nuevo Rol para una vieja proteína: Fibrinógeno. Editorial Académica EspañolaGoogle Scholar
  38. 38.
    Jiménez-Rosales A, Amaya-Chávez A, Domínguez García MV, Camarillo-Romero E, Huitrón Bravo GG, Cruz AM (2013) Association of inflammatory and oxidative stress biomarkers in subjects with cardiovascular risk. Am J Ther 20(4):422–431PubMedCrossRefGoogle Scholar
  39. 39.
    Scribano MP, Baez MC, Becerra F, Tarán M, Signorini F, Balceda AG, Moya M (2014) Effects of atorvastatin on oxidative stress biomarkers and mitochondrial morphofunctionality in hyperfibrinogenemia-induced atherogenesis. Adv Med 2014. Article ID 947258:1–6CrossRefGoogle Scholar
  40. 40.
    Garagiola ML, Tarán M, Scribano MP, Balceda A, García E, Fonseca I, Moya M, Baez MC (2016) Myeloperoxidase as an indicator of oxidative stress in metabolic syndrome. Argent J Cardiol 84(6):514–518Google Scholar
  41. 41.
    Aouacheri O, Saka S, Krim M, Messaadia A, Maidi I (2015) The investigation of the oxidative stress-related parameters in type 2 diabetes mellitus. Can J Diabetes 39(1):44–49PubMedCrossRefGoogle Scholar
  42. 42.
    Wang Y-X (ed) (2017) Pulmonary vasculature redox signaling in health and disease, vol 967. Springer, ChamGoogle Scholar
  43. 43.
    Sena CM, Pereira AM, Seiça R (2013) Endothelial dysfunction – a major mediator of diabetic vascular disease. Biochim Biophys Acta 1832(12):2216–2231PubMedCrossRefGoogle Scholar
  44. 44.
    Yubero-Serrano EM, Delgado-Lista J, Peña-Orihuela P, Perez-Martinez P, Fuentes F, Marin C et al (2013) Oxidative stress is associated with the number of components of metabolic syndrome: LIPGENE study. Exp Mol Med 45:e28. Scholar
  45. 45.
    Mahendra JV, Kumar SD, Anuradha TS, Prashanth T, Nagaraj RS, Vishali V (2015) Plasma fibrinogen in type 2 diabetic patients with metabolic syndrome and its relation with ischemic heart disease (IHD) and retinopathy. J Clin Diagn Res 9(1):BC18–BC21PubMedPubMedCentralGoogle Scholar
  46. 46.
    Chen YR, Zweier JL (2014) Cardiac mitochondria and reactive oxygen species generation. Circ Res 114(3):524–537PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Giovanni B, Rodriguez R (2008) Ultrastructure of the mitochondrion and its bearing on function and bioenergetics. Antioxid Redox Signal 10(8):1313–1342CrossRefGoogle Scholar
  48. 48.
    Chistiakov DA, Shkurat TP, Melnichenko AA, Grechko AV, Orekhov AN (2018) The role of mitochondrial dysfunction in cardiovascular disease: a brief review. Ann Med 50(2):121–127PubMedCrossRefGoogle Scholar
  49. 49.
    Hulsmans M, Van Dooren E, Holvoet P (2012) Mitochondrial reactive oxygen species and risk of atherosclerosis. Curr Atheroscler Rep 14(3):264–276PubMedCrossRefGoogle Scholar
  50. 50.
    Vichova T, Motovska Z (2013) Oxidative stress: predictive marker for coronary artery disease. Exp Clin Cardiol 18(2):e88–e91PubMedPubMedCentralGoogle Scholar
  51. 51.
    Chong SJ, Low IC, Pervaiz S (2014) Mitochondrial ROS and involvement of Bcl-2 as a mitochondrial ROS regulator. Mitochondrion 19(Pt A):39–48PubMedCrossRefGoogle Scholar
  52. 52.
    Takeuchi A, Kim B, Matsuoka S (2015) The destiny of Ca2+ released by mitochondria. J Physiol Sci 65(1):11–24PubMedCrossRefGoogle Scholar
  53. 53.
    Radi R (2013) Protein tyrosine nitration: biochemical mechanisms and structural basis of functional effects. Acc Chem Res 46(2):550–559PubMedCrossRefGoogle Scholar
  54. 54.
    Oliveira PJ (ed) (2018) Mitochondrial biology and experimental therapeutics. Springer Nature, ChamGoogle Scholar
  55. 55.
    Newton BW, Cologna SM, Moya C, Russell DH, Russell WK, Jayaraman A (2011) Proteomic analysis of 3T3-L1 adipocyte mitochondria during differentiation and enlargement. J Proteome Res 10(10):4692–4702PubMedCrossRefGoogle Scholar
  56. 56.
    Sil R, Chakraborti AS (2016) Oxidative inactivation of liver mitochondria in high fructose diet-induced metabolic syndrome in rats: effect of glycyrrhizin treatment. Phytother Res 30(9):1503–1512PubMedCrossRefGoogle Scholar
  57. 57.
    Shen GX (2012) Mitochondrial dysfunction, oxidative stress and diabetic cardiovascular disorders. Cardiovasc Hematol Disord Drug Targets 12(2):106–112PubMedCrossRefGoogle Scholar
  58. 58.
    Faria A, Persaud SJ (2017) Cardiac oxidative stress in diabetes: mechanisms and therapeutic potential. Pharmacol Ther 172:50–62PubMedCrossRefGoogle Scholar
  59. 59.
    Peinado JR, Diaz-Ruiz A, Frühbeck G, Malagon MM (2014) Mitochondria in metabolic disease: getting clues from proteomic studies. Proteomics 14(4–5):452–466PubMedCrossRefGoogle Scholar
  60. 60.
    Zorov DB, Juhaszova M, Sollott SJ (2014) Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev 94(3):909–950PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Yayan J (2013) Emerging families of biomarkers for coronary artery disease: inflammatory mediators. Vasc Health Risk Manag 9:435–456PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Voudris KV, Chanin J, Feldman DN, Charitakis K (2015) Novel inflammatory biomarkers in coronary artery disease: potential therapeutic approaches. Curr Med Chem 22(22):2680–2689PubMedCrossRefGoogle Scholar
  63. 63.
    Renna N, Vázquez M, González S, Lama C, Cruzado M, Miatello R (2007) Expresión vascular de factores de transcripción proinflamatorios en un modelo de Síndrome Metabólico. Rev Argent Cardiol 75:36–41Google Scholar
  64. 64.
    Evaluation and Treatment of High Blood Cholesterol in Adults (2001) Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 285:2486–2497CrossRefGoogle Scholar
  65. 65.
    National Diabetes Data Group (1979) Classification and diagnosis of diabetes and other categories of glucose intolerance. Diabetes 28:1039–1057CrossRefGoogle Scholar
  66. 66.
    Wallace TM, Levy JC, Matthews DR (2004) Use and abuse of HOMA modeling. Diabetes Care 27:1487–1495PubMedCrossRefGoogle Scholar
  67. 67.
    Nakagawa T, Hu H, Zharikov S, Tuttle KR, Short RA, Glushakova O, Ouyang X, Feig DI, Block ER, Herrera-Acosta J, Patel JM, Johnson RJ (2006) A causal role for uric acid in fructose-induced metabolic syndrome. Am J Phys Renal Phys 290(3):625–631Google Scholar
  68. 68.
    Stanhope KL (2012) Role of fructose-containing sugars in the epidemics of obesity and metabolic syndrome. Annu Rev Med 63:329–343PubMedCrossRefGoogle Scholar
  69. 69.
    Bursać BN, Vasiljević AD, Nestorović NM, Veličković NA, Vojnović Milutinović DD, Matić GM, Djordjevic AD (2014) High-fructose diet leads to visceral adiposity and hypothalamic leptin resistance in male rats–do glucocorticoids play a role? J Nutr Biochem 25(4):446–455PubMedCrossRefGoogle Scholar
  70. 70.
    Qu HQ, Li Q, Rentfro AR, Fisher-Hoch SP, McCormick JB (2011) The definition of insulin resistance using HOMA-IR for Americans of Mexican descent using machine learning. PLoS One 6(6):e21041PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Simmons RK, Alberti KG, Gale EA, Colagiuri S, Tuomilehto J, Qiao Q, Ramachandran A, Tajima N, Brajkovich MI, Ben Nakhi A, Reaven G, Hama SB, Mendis S, Roglic G (2010) The metabolic syndrome: useful concept or clinical tool? Report of a WHO expert consultation. Diabetologia 53(4):600–605PubMedCrossRefGoogle Scholar
  72. 72.
    Maury E, Brichard SM (2010) Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome. Mol Cell Endocrinol 314(1):1–16PubMedCrossRefGoogle Scholar
  73. 73.
    Thaler JP, Yi C-X, Schur EA et al (2012) Obesity is associated with hypothalamic injury in rodents and humans. J Clin Invest 122(1):153–162PubMedCrossRefGoogle Scholar
  74. 74.
    Caimi G, Lo Presti R, Montana M, Noto D, Canino B, Averna MR, Hopps E (2014) Lipid peroxidation, nitric oxide metabolites, and their ratio in a group of subjects with metabolic syndrome. Oxidative Med Cell Longev 824756:2014Google Scholar
  75. 75.
    Rosenson RS, Brewer HB Jr, Davidson WS, Fayad ZA, Fuster V (2012) Cholesterol efflux and atheroprotection: advancing the concept of reverse cholesterol transport. Circulation 125(15):1905–1919PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Gomaraschi M, Ossoli A, Pozzi S, Nilsson P, Cefalù A, Averna M, Kuivenhoven J, Hovingh G, Veglia F, Franceschini G, Calabresi L (2014) 133 eNOS activation by HDL is impaired in genetic CETP deficiency. PLoS One 9(5):e95925PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Rodriguez AD (2014) The fixed combination of pravastatin and fenofibrate: what can it provide? Clin Investig Arterioscler 26(1):12–16Google Scholar
  78. 78.
    Besler C, Heinrich K, Rohrer L, Doerries C, Riwanto M et al (2011) Mechanisms underlying adverse effects of HDL on eNOS-activating pathways in patients with coronary artery disease. J Clin Invest 121(7):2693–2708PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Gomaraschi M et al (2014) eNOS activation by HDL is impaired in genetic CETP deficiency. PLoS One 9(5):e95925PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Gaggini M, Morelli M, Buzzigoli E, DeFronzo RA, Bugianesi E, Gastaldelli A (2013) Non-alcoholic fatty liver disease (NAFLD) and its connection with insulin resistance, dyslipidemia, atherosclerosis and coronary heart disease. Nutrients 5(5):1544–1560PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Bhaswant M, Poudyal H, Mathai ML, Ward LC, Mouatt P, Brown L (2015) Green and black cardamom in a diet-induced rat model of metabolic syndrome. Nutrients 7(9):7691–7707PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Ozturk ZA, Kadayifci A (2014) Insulin sensitizers for the treatment of non-alcoholic fatty liver disease. World J Hepatol 6(4):199–206PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Abd El-Kader SM, El-Den Ashmawy EM (2015) Non-alcoholic fatty liver disease: the diagnosis and management. World J Hepatol 7(6):846–858PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Ratnoff OD, Menzie AC (1957) A new method for the determination of fibrinogen in small samples of plasma. J Lab Clin Med 37:316–320Google Scholar
  85. 85.
    Moncada S, Palmer RM, Higgs EA (1989) The biological significance of nitric oxide formation from L-arginine. Biochem Soc Trans 17(4):642–644PubMedCrossRefGoogle Scholar
  86. 86.
    Woolliams JA, Wiener G, Anderson PH, McMurray CH (1983) Variation in the activities of glutathione peroxidase and superoxide dismutase and in the concentration of copper in the blood in various breed crosses of sheep. Res Vet Sci 34:253–256PubMedCrossRefGoogle Scholar
  87. 87.
    Vanhoutte PM, Shimokawa H, Feletou M, Tang EH (2017) Endothelial dysfunction and vascular disease – a 30th anniversary update. Acta Physiol (Oxford) 219(1):22–96CrossRefGoogle Scholar
  88. 88.
    Sabater-Lleal M, Huang J, Chasman D, Naitza S, Dehghan A, Johnson AD (2013) Multiethnic meta-analysis of genome-wide association studies in >100 000 subjects identifies 23fibrinogenassociated loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease. Circulation 128(12):1310–1324PubMedCrossRefGoogle Scholar
  89. 89.
    El Assar M, Ruiz de Adana JC, Angulo J, Pindado Martínez ML, Hernández MA, Rodríguez-Mañas L (2013) Preserved endothelial function in human obesity in the absence of insulin resistance. J Transl Med 11:263. Scholar
  90. 90.
    Feoli AM, Macagnan FE, Piovesan CH, Bodanese LC, Siqueira IR (2014) Xanthine oxidase activity is associated with risk factors for cardiovascular disease and inflammatory and oxidative status markers in metabolic syndrome: effects of a single exercise session. Oxidative Med Cell Longev 2014:1–8. 587083. Scholar
  91. 91.
    Smith BW, Adams LA (2011) Non-alcoholic fatty liver disease. Crit Rev Clin Lab Sci 48(3):97–113PubMedCrossRefGoogle Scholar
  92. 92.
    Manco M (2011) Metabolic syndrome in childhood from impaired carbohydrate metabolism to nonalcoholic fatty liver disease. J Am Coll Nutr 30(5):295–303PubMedCrossRefGoogle Scholar
  93. 93.
    Castro GS, Cardoso JF, Vannucchi H, Zucoloto S, Jordão AA (2011) Fructose and NAFLD: metabolic implications and models of induction in rats. Acta Cir Bras 26(2):45–50PubMedCrossRefGoogle Scholar
  94. 94.
    Tarán Mariana D, Baez María C, de La Paz Scribamo Parada M, Balceda A, Sergio B, Miriam B, Mónica M (2018) Experimental model of oxidative stress markers in subclinical atherogenesis associated with metabolic syndrome. SM J Cardiol Cardiovasc Dis 4(1):1021Google Scholar
  95. 95.
    Cao YX, Li LP (2014) Relationship of non-alcoholic steatohepatitis with arterial endothelial function and atherosclerosis. Zhonghua Gan Zang Bing Za Zhi 22(3):205–208PubMedGoogle Scholar
  96. 96.
    Van der Poorten D, Samer CF, Ramezani-Moghadam M, Coulter S, Kacevska M, Schrijnders D, Wu LE, McLeod D, Bugianesi E, Komuta M et al (2013) Hepatic fat loss in advanced nonalcoholic steatohepatitis: are alterations in serum adiponectin the cause? Hepatology (Baltim) 57:2180–2188CrossRefGoogle Scholar
  97. 97.
    Weiß J, Rau M, Geier A (2014) Non-alcoholic fatty liver disease: epidemiology, clinical course, investigation, and treatment. Dtsch Arztebl Int 111(26):447–452PubMedPubMedCentralGoogle Scholar
  98. 98.
    Nassir F, Ibdah JA (2014) Role of mitochondria in nonalcoholic fatty liver disease. Int J Mol Sci 15(5):8713–8742PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Wong R, Aijaz Ahmed A (2014) Obesity and non-alcoholic fatty liver disease: disparate associations among Asian populations. World J Hepatol 6(5):263–273PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Tilg H, Moschen AR (2010) Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis. Hepatology 52(5):1836–1846PubMedCrossRefGoogle Scholar
  101. 101.
    Torre-Villalvazo I, Bunt AE, Alemán G, Marquez-Mota CC, Diaz-Villaseñor A, Noriega LG, Estrada I, Figueroa-Juárez E et al (2018) Adiponectin synthesis and secretion by subcutaneous adipose tissue is impaired during obesity by endoplasmic reticulum stress. J Cell Biochem 119(7):5970–5984PubMedCrossRefGoogle Scholar
  102. 102.
    Bellafante E, Murzilli S, Salvatore L, Latorre D, Villani G, Moschetta A (2013) Hepatic-specific activation of peroxisome proliferator-activated receptor γ coactivator-1β protects against steatohepatitis. Hepatology 57(4):1343–1356PubMedCrossRefGoogle Scholar
  103. 103.
    Silva AKS, Peixoto CA (2018) Role of peroxisome proliferator-activated receptors in non-alcoholic fatty liver disease inflammation. Cell Mol Life Sci 75:2951–2961. [Epub ahead of print]CrossRefPubMedGoogle Scholar
  104. 104.
    Novo S, Peritore A, Guarneri FP, Corrado E, Macaione F, Evola S, Novo G (2012) Metabolic syndrome (MetS) predicts cardio and cerebrovascular events in a twenty years follow-up. A prospective study. Atherosclerosis 223(2):468–472PubMedCrossRefGoogle Scholar
  105. 105.
    Bernabé García J, Zafrilla Rentero P, Mulero Cánovas J, Gómez Jara P, Leal Hernández M, Abellán Alemán J (2014) Biochemical and nutritional markers and antioxidant activity in metabolic syndrome. Endocrinol Nutr 61(6):302–308PubMedCrossRefGoogle Scholar
  106. 106.
    Chistiakov DA, Sobenin IA, Bobryshev YV, Orekhov AN (2012) Mitochondrial dysfunction and mitochondrial DNA mutations in atherosclerotic complications in diabetes. World J Cardiol 4(5):148–156PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Rocha M, Apostolova N, Herance JR, Rovira-Llopis S, Hernandez-Mijares A, Victor VM (2014) Perspectives and potential applications of mitochondria-targeted antioxidants in cardiometabolic diseases and type 2 diabetes. Med Res Rev 34(1):160–189PubMedCrossRefGoogle Scholar
  108. 108.
    Lim S, Rashid MA, Jang M, Kim Y, Won H, Lee J, Woo JT, Kim YS, Murphy MP, Ali L, Ha J, Kim SS (2011) Mitochondria-targeted antioxidants protect pancreatic β-cells against oxidative stress and improve insulin secretion in glucotoxicity and glucolipotoxicity. Cell Physiol Biochem 28(5):873–886PubMedCrossRefGoogle Scholar
  109. 109.
    Han D, Canali R, Rettori D, Kaplowitz N (2003) Effect of glutathione depletion on sites and topology of superoxide and hydrogen peroxide production in mitochondria. Mol Pharmacol 64(5):1136–1144PubMedCrossRefGoogle Scholar
  110. 110.
    Parra V, Verdejo H, del Campo A, Pennanen C, Kuzmicic J, Iglewski M et al (2011) The complex interplay between mitochondrial dynamics and cardiac metabolism. J Bioenerg Biomembr 43:47–51PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Marín-García J, Goldenthal MJ (2002) La mitocondria y el corazón. Rev Esp Cardiol 55(12):1293–1310PubMedCrossRefGoogle Scholar
  112. 112.
    Kuzmicic J, Del Campo A, López-Crisosto C, Morales PE, Pennanen C, Bravo-Sagua R et al (2011) Mitochondrial dynamics: a potential new therapeutic target for heart failure. Rev Esp Cardiol (English Edition) 64(10):916–923CrossRefGoogle Scholar
  113. 113.
    Hirokawa N, Takemura R (2005) Molecular motors and mechanisms of directional transport in neurons. Nat Rev Neurosci 6:201–214PubMedCrossRefGoogle Scholar
  114. 114.
    Hollenbeck PJ, Saxton WM (2005) The axonal transport of mitochondria. J Cell Sci 118(23):5411–5419PubMedPubMedCentralCrossRefGoogle Scholar
  115. 115.
    Germain M, Mathai JP, McBride HM, Shore GC (2005) Endoplasmic reticulum BIK initiates DRP1-regulated remodelling of mitochondrial cristae during apoptosis. EMBO J 24(8):1546–1556PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Seppet E et al (2009) Mitochondria and energetic depression in cell pathophysiology. Int J Mol Sci 10(5):2252–2303PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Stowe DF, Camara AK (2009) Mitochondrial reactive oxygen species production in excitable cells: modulators of mitochondrial and cell function. Antioxid Redox Signal 11(6):1373–1414PubMedPubMedCentralCrossRefGoogle Scholar
  118. 118.
    Quinlan CL, Perevoshchikova IV, Hey-Mogensen M, Orr AL, Branda MD (2013) Sites of reactive oxygen species generation by mitochondria oxidizing different substrates. Redox Biol 1(1):304–312PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Quinlan CL, Orr AL, Perevoshchikova IV, Treberg JR, Ackrell BA, Brand MD (2012) Mitochondrial complex II can generate reactive oxygen species at high rates in both the forward and reverse reactions. J Biol Chem 287(32):27255–27264PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    Fisher-Wellman KH, Neufer PD (2012) Linking mitochondrial bioenergetics to insulin resistance via redox biology. Trends Endocrinol Metab 23(3):142–153PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Koju N et al (2019) Pharmacological strategies to lower crosstalk between nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and mitochondria. Biomed Pharmacother 111:1478–1498PubMedCrossRefGoogle Scholar
  122. 122.
    Yan LJ (2014) Pathogenesis of chronic hyperglycemia: from reductive stress to oxidative stress. J Diabetes Res 2014:1–11. 137919. Scholar
  123. 123.
    Rector RS, Uptergrove GM, Borengasser SJ, Mikus CR, Morris EM, Naples SP, Laye MJ, Laughlin MH, Booth FW, Ibdah JA, Thyfault JP (2010) Changes in skeletal muscle mitochondria in response to the development of type 2 diabetes or prevention by daily wheel running in hyperphagic OLETF rats. Am J Physiol Endocrinol Metab 298(6):1179–1187CrossRefGoogle Scholar
  124. 124.
    Miller MW, Knaub LA, Olivera-Fragoso LF, Keller AC, Balasubramaniam V, Watson PA, Reusch JE (2013) Nitric oxide regulates vascular adaptive mitochondrial dynamics. Am J Physiol Heart Circ Physiol 304(12):H1624–H1633PubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Madamanchi NR, Runge MS (2007) Mitochondrial dysfunction in atherosclerosis. Circ Res 100(4):460–473PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • María del Carmen Baez
    • 1
  • Mariana Tarán
    • 1
  • Mónica Moya
    • 1
    • 2
  • María de la Paz Scribano Parada
    • 1
  1. 1.Cardiovascular Biomarkers Laboratory, Cátedra de Física Biomédica, Facultad de Ciencias MédicasUniversidad Nacional de CórdobaCórdobaArgentina
  2. 2.Física Biomédica, Ciencias MédicasUniversidad Nacional de La RiojaLa RiojaArgentina

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