Oxidative stress is believed to be a major contributory factor in the development of non alcoholic fatty liver disease (NAFLD), the most common liver disorder worldwide. In this study, the effects of high fat diet-induced NAFLD on Coenzyme Q (CoQ) metabolism and plasma oxidative stress markers in rats were investigated. Rats were fed a standard low fat diet (control) or a high fat diet (57% metabolizable energy as fat) for 18 weeks. The concentrations of total (reduced + oxidized) CoQ9 were increased by > 2 fold in the plasma of animals fed the high fat diet, while those of total CoQ10 were unchanged. Reduced CoQ levels were raised, but oxidized CoQ levels were not, thus the proportion in the reduced form was increased by about 75%. A higher percentage of plasma CoQ9 as compared to CoQ10 was in the reduced form in both control and high fat fed rats. Plasma protein thiol (SH) levels were decreased in the high fat-fed rats as compared to the control group, but concentrations of lipid hydroperoxides and low density lipoprotein (LDL) conjugated dienes were unchanged. These results indicate that high fat diet-induced NAFLD in rats is associated with altered CoQ metabolism and increased protein, but not lipid, oxidative stress.
References
[1]
Adams, L.A.; Angulo, P. Recent concepts in non-alcoholic fatty liver disease. Diabet. Med 2005, 22, 1129–1133.
[2]
Svegliati-Baroni, G.; Candelaresi, C.; Saccomanni, S.; Ferretti, G.; Bachetti, T.; Marzioni, M.; Minicis, S.D.; Nobili, L.; Salzano, R.; Omenetti, A.; et al. A model of insulin resistance and nonalcoholic steatohepatitis in rats. Am. J. Pathol 2006, 169, 846–860.
[3]
Videla, L.A.; Rodrigo, R.; Araya, J.; Poniachik, J. Insulin resistance and oxidative stress interdependency in non-alcoholic fatty liver disease. Trends Mol. Med 2006, 12, 555–558.
[4]
Day, C.P.; James, O.F.W. Steatohepatitis: A tale of two “hits”? Gastroenterology 1998, 114, 842–845.
[5]
Anstee, Q.M.; Goldin, R.D. Mouse models in non-alcoholic fatty liver disease and steatohepatitis research. Int. J. Exp. Pathol 2006, 87, 1–16.
[6]
Grattagliano, I.; Palmieri, V.O.; Portincasa, P.; Moschetta, A.; Palasciano, G. Oxidative stress-induced risk factors associated with the metabolic syndrome: A unifying hypothesis. J. Nutr. Biochem 2008, 19, 491–504.
[7]
Videla, L.A.; Rodrigo, R.; Araya, J.; Poniachik, J. Oxidative stress and depletion of hepatic long-chain polyunsaturated fatty acids may contribute to nonalcoholic fatty liver disease. Free Radic. Biol. Med 2004, 37, 1499–1507.
[8]
Videla, L.A.; Rodrigo, R.N.; Orellana, M.; Fernandez, V.; Tapia, G.; Quinones, L.; Varela, N.; Contreras, J.; Lazarte, R.; Csendes, A.; et al. Oxidative stress-related parameters in the liver of non-alcoholic fatty liver disease patients. Clin. Sci 2004, 106, 261–268.
[9]
Day, C.P. Non-alcoholic fatty liver disease: Current concepts and management strategies. Clin. Med 2006, 6, 19–25.
[10]
Araya, J.; Rodrigo, R.N.; Videla, L.A.; Thielemann, L.; Orellana, M.; Pettinelli, P.; Poniachik, J. Increase in long-chain polyunsaturated fatty acid n-6/n-3 ratio in relation to hepatic steatosis in patients with non-alcoholic fatty liver disease. Clin. Sci 2004, 106, 635–643.
Buqué, X.; Martínez, M.J.; Cano, A; Miquilena-Colina, M.E.; García-Monzón, C.; Aspichueta, P.; Ochoa, B. A subset of dysregulated metabolic and survival genes is associated with severity of hepatic steatosis in obese Zucker rats. J. Lipid Res. 2010, 51, 500–513.
[13]
Bentinger, M.; Brismar, K.; Dallner, G. The antioxidant role of coenzyme Q. Mitochondrion 2007, 7, S41–S50.
[14]
Petrosillo, G.; Portincasa, P.; Grattagliano, I.; Casanova, G.; Matera, M.; Ruggiero, F.M.; Ferri, D.; Paradies, G. Mitochondrial dysfunction in rat with nonalcoholic fatty liver: Involvement of complex I, reactive oxygen species and cardiolipin. Biochim. Biophys. Acta 2007, 1767, 1260–1267.
[15]
Safwat, G.M.; Pisanò, S.; D’Amore, E.; Borioni, G.; Napolitano, M.; Kamal, A.A.; Ballanti, P.; Botham, K.M.; Bravo, E. Induction of non-alcoholic fatty liver disease and insulin resistance by feeding a high-fat diet in rats: Does coenzyme Q monomethyl ether have a modulatory effect? Nutrition 2009, 25, 1157–1168.
[16]
Koteish, A.; Diehl, A. Animal models of steatosis. Semin. Liver Dis 2001, 21, 89–104.
[17]
Lieber, C.S.; Leo, M.A.; Mak, K.M.; Xu, Y.; Cao, Q.; Ren, C.; Ponomarenko, A.; de Carli, L.M. Model of nonalcoholic steatohepatitis. Am. J. Clin. Nutr 2004, 79, 502–509.
[18]
Cano, A.; Ciaffoni, F.; Safwat, G.M.; Aspichueta, P.; Ochoa, B.; Bravo, E.; Botham, K.M. Hepatic very low density lipoprotein assembly is disturbed in a rat model of non alcoholic fatty liver disease: Is there a role for dietary Coenzyme Q? J. Appl. Physiol 2009, 107, 707–717.
Sorbi, D.; Boyton, J.; Lindor, K.D. The ratio of aspartate aminotransferase to alanine aminotransferase: Potential value in differentiating nonalcoholic steatohepatitis from alcoholic liver disease. Am. J. Gastroenterol 1999, 94, 1018–1022.
[21]
Houstis, N.; Rosen, E.D.; Lander, E.S. Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature 2006, 440, 944–948.
[22]
Hermans, N.; Cos, P.; de Meyer, G.R.Y.; Maes, L.; Pieters, L.; Vanden Berghe, D.; Vlietinck, A.J.; de Bruyne, T. Study of potential systemic oxidative stress animal models for the evaluation of antioxidant activity: Status of lipid peroxidation and fat-soluble antioxidants. J. Pharm. Pharmacol 2007, 59, 131–136.
[23]
Ferreira, F.M.; Sei？a, R.; Oliveira, P.J.; Coxito, P.M.; Moreno, A.J.; Palmeira, C.M.; Santos, M.S. Diabetes induces metabolic adaptations in rat liver mitochondria: Role of coenzyme Q and cardiolipin contents. Biochim. Biophys. Acta 2003, 1639, 113–120.
[24]
Kohli, R.; Kirby, M.; Xanthakos, S.A.; Softic, S.; Feldstein, A.E.; Saxena, V.; Tang, P.H.; Miles, L.; Miles, M.V.; Balistreri, W.F.; et al. High-fructose, medium chain trans fat diet induces liver fibrosis and elevates plasma coenzyme Q9 in a novel murine model of obesity and nonalcoholic steatohepatitis. Hepatology 2010, 52, 934–944.
[25]
Ernster, L.; Dallner, G. Biochemical, physiological and medical aspects of ubiquinone formation. Biochim. Biophys. Acta 1995, 1271, 195–204.
[26]
Turunen, M.; Olsson, J.; Dallner, G. Metabolism and function of coenzyme Q. Biochim. Biophys. Acta 2004, 1660, 171–199.
[27]
Quiles, J.A.; Huertas, J.R.; Manas, M.; Battino, M.; Cassinello, M.; Littarru, G.P.; Lenaz, G.; Mataix, F.J. Peroxidative extent and coenzyme Q levels in the rat: Influence of physical training and dietary fats. Mol. Aspects Med 1994, 15, 89–95.
[28]
Ahmed, U.; Redgrave, T.G.; Oates, P.S. Effect of dietary fat to produce non-alcoholic fatty liver in the rat. J. Gastroenterol. Hepatol 2009, 24, 1463–1471.
[29]
Zhu, M.J.; Sun, L.J.; Liu, Y.Q.; Feng, Y.L.; Tong, H.T.; Hu, Y.H.; Zhao, Z. Blood F2-isoprostanes are significantly associated with abnormalities of lipid status in rats with steatosis. World Gastroenterol. J 2008, 14, 4677–4683.
[30]
Folch, J.; Lees, M.; Stanley, G.H.S. A simple method for the isolation and purification of total lipides from animal tissues. J. Biol. Chem 1957, 226, 497–509.
[31]
Friedewald, W.T.; Levy, R.I.; Fredrickson, D.S. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin. Chem 1972, 18, 499–502.
[32]
Pinchuk, I.; Lichtenberg, D. The mechanism of action of antioxidants against lipoprotein peroxidation, evaluation based on kinetic experiments. Prog. Lipid Res 2002, 41, 279–314.
[33]
Bradford, M. A sensitive method for quantitation of microgram quantities of protein utilizing the principle of dye-binding. Anal. Biochem 1976, 72, 248–254.
[34]
Balercia, G.; Mosca, F.; Mantero, F.; Boscaro, M.; Mancini, A.; Ricciardo-Lamonica, G.; Littarru, G. Coenzyme Q10 supplementation in infertile men with idiopathic asthenozoospermia: An open, uncontrolled pilot study. Fertil. Steril 2004, 81, 93–98.
[35]
Nierenberg, D.W.; Lester, D.C. Determination of vitamins A and E in serum and plasma using a simplified clarification method and high-performance liquid chromatography. J. Chromatogr 1985, 345, 275–284.
[36]
Pfeiffer, C.M.; Huff, D.L.; Gunter, E.W. Rapid and accurate HPLC assay for plasma total homocysteine and cysteine in a clinical laboratory setting. Clin. Chem 1999, 45, 290–292.
[37]
Vassalle, C.; Boni, C.; di Cecco, P.; Ndreu, R.; Zucchelli, G.C. Automation and validation of a fast method for the assessment of in vivo oxidative stress levels. Clin. Chem. Lab. Med 2006, 44, 1372–1375.
[38]
Anderson, M.E. Determination of glutathione and glutathione disulfide in biological samples. Methods Enzymol 1985, 113, 548–555.
