Mitochondrial dysfunction in non-alcoholic fatty liver disease and insulin resistance: Cause or consequence?

References

• Tilg H, Diehl AM. Cytokines in alcoholic and nonalcoholic steatohepatitis. N Engl J Med 2000;343:1467–1476.
   PubMed Web of Science ®Google Scholar
• Agulo P. Nonalcoholic fatty liver disease. N Engl J Med 2002;346:1221–1231.
   Google Scholar
• Wang Y, Lobstein T. Worldwide trends in childhood overweight and obesity. Int J Pediatr Obes 2006;1:11–25.
   PubMed Web of Science ®Google Scholar
• Pessayre D, Fromenty B. NASH: a mitochondrial disease. J Hepatol 2005;42:928–940.
   PubMed Web of Science ®Google Scholar
• Rolo AP, Teodoro JS, Palmeira CM. Role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis. Free Rad Biol Med 2012;52:59–69.
   PubMed Web of Science ®Google Scholar
• Gonzalez-Franquesa A, De Nigris V, Lerin C, Garcia-Roves PM. Skeletal muscle mitochondrial function/dysfunction and type 2 diabetes. In: Cseri J (ed.). Skeletal muscle: from myogenesis to clinical relations. Croatia: InTech.; 2012 pp. 257–292.
   Google Scholar
• Goldstein B, Mahadev K, Wu X. Redox paradox insulin action is facilitated by insulin-stimulated reactive oxygen species with multiple potential signaling targets. Diabetes 2005;54:311–321.
   PubMed Web of Science ®Google Scholar
• Evans JL, Goldfine ID, Maddux BA, Grodsky GM. Oxidative stress and stress-activated signaling patways: a unifying hypothesis of type 2 diabetes. Endocr Rev 2002;23: 599–622.
   PubMed Web of Science ®Google Scholar
• Mari M, Colell A, Morales A, vonMontfort A, Garcia-Ruiz C, Fernandez-Checa JC. Redox control of liver function in health and disease. Antioxid Redox Signal 2010;12: 1295–1331.
   PubMed Web of Science ®Google Scholar
• Browning JD, Horton JD. Molecular mediators of hepatic steatosis and liver injury. J Clin Invest 2004;114:147–152.
   PubMed Web of Science ®Google Scholar
• Horton JD, Goldstein JL, Brown MS. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest 2002;109:1125–1131.
   PubMed Web of Science ®Google Scholar
• Abu-Elheiga L, Brinkley WR, Zhong L, Chirala SS, Woldegiorgis G, Wakil SJ. The subcellular localization of acetyl-CoA carboxylase 2. Proc Natl Acad Sci 2000;97: 1444–1449.
   PubMed Web of Science ®Google Scholar
• McGarry JD, Mannaerts GP, Foster DW. A possible role for malonyl-CoA in the regulation of hepatic fatty acid oxidation and ketogenesis. J Clin Invest 1977;60:265–270.
   PubMed Web of Science ®Google Scholar
• Goldstein JL, Brown MS. Regulation of the mevalonate pathway. Nature 1990;343:425–430.
   PubMed Web of Science ®Google Scholar
• Brown MS, Goldstein JL. Multivalent feedback regulation of HMG CoA reductase, a control mechanism coordinating isoprenoid synthesis and cell growth. J Lipid Res 1980;21: 505–517.
   PubMed Web of Science ®Google Scholar
• Rawson RB, DeBose-Boyd R, Goldstein JL, Brown MS. Failure to cleave sterol regulatory element-binding proteins (SREBPs) causes cholesterol auxotrophy in Chinese hamster ovary cells with genetic absence of SREBP cleavage-activating protein. J Biol Chem 1999;274:28549–28556.
   PubMed Web of Science ®Google Scholar
• Ozcan U, Cao Q, Yilmaz E, Lee AH, Iwakoshi NN, Ozdelen E, et al. Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes. Science 2004;306:457–461.
   PubMed Web of Science ®Google Scholar
• Puri P, Mirshahi F, Cheung O, Natarajan R, Maher JW, Kellum JM, Sanyal AJ. Activation and dysregulation of the unfolded protein response in nonalcoholic fatty liver disease. Gastroenterology 2008;134:568–576.
   PubMed Web of Science ®Google Scholar
• Henkel AS, Elias MS, Green RM. Homocysteine supplementation attenuates the unfolded protein response in a murine nutritional model of steatohepatitis. J Biol Chem 2009; 284:31807–31816.
   PubMed Web of Science ®Google Scholar
• Yang JS, Kim JT, Jeon J, Park HS, Kang GH, Park KS, et al. Changes in hepatic gene expression upon oral administration of taurine conjugated ursodeoxycholic acid in ob/ob mice. PLoS One 2010;5:e13858.
   Google Scholar
• Sleigh A, Raymond-Barker P, Thackray K, Porter D, Hatunic M, Vottero A, et al. Mitochondrial dysfunction in patients with primary congenital insulin resistance. J Clin Invest 2011;121:2457–2461.
   PubMed Web of Science ®Google Scholar
• Pérez-Carreras M, Del Hoyo P, Martín MA, Rubio JC, Martín A, Castellano G, et al. Defective hepatic mitochondrial respiratory chain in patients with nonalcoholic steatohepatitis. Hepatology 2003;38:999–1007.
   PubMed Web of Science ®Google Scholar
• Orellana-Gavaldà JM, Herrero L, Malandrino MI, Pañeda A, Sol Rodríguez-Peña M, Petry H, et al. Molecular therapy for obesity and diabetes based on a long-term increase in hepatic fatty-acid oxidation. Hepatology 2011;53:821–832.
   PubMed Web of Science ®Google Scholar
• Keung W, Ussher JR, Jaswal JS, Raubenheimer M, Lam VH, Wagg CS, Lopaschuk GD. Inhibition of carnitine palmitoyltransferase-1 activity alleviates insulin resistance in diet- induced obese mice. Diabetes 2013;62:711–720.
   PubMed Web of Science ®Google Scholar
• Day CP, James OF. Steatohepatitis: a tale of two “hits”?Gastroenterology 1998;114:842–845.
   PubMed Web of Science ®Google Scholar
• Marí M, Caballero F, Colell A, Morales A, Caballeria J, Fernandez A, et al. Mitochondrial free cholesterol loading sensitizes to TNF- and Fas-mediated steatohepatitis. Cell Metab 2006;4:185–198.
   PubMed Web of Science ®Google Scholar
• Garcia-Ruiz C, Mari M, Colell A, Morales A, Caballero F, Montero J, et al. Mitochondrial cholesterol in health and disease. Histol Histopathol 2009;24:117–132.
   PubMed Web of Science ®Google Scholar
• Feldstein AE, Werneburg NW, Canbay A, Guicciardi ME, Bronk SF, Rydzewski R, et al. Free fatty acids promotes hepatic lipotoxicity by stimulating TNF-alpha expression via a lysosomal pathway. Hepatology 2004;40:185–194.
   PubMed Web of Science ®Google Scholar
• Borradaile NM, Han X, Harp JD, Gale SE, Ory DS, Schaffer JE, Disruption of endoplasmic reticulum structure and integrity in lipotoxic cell death. J Lipid Res 2006;47: 2726–2737.
   PubMed Web of Science ®Google Scholar
• Srivastava, S, Chan C. Hydrogen peroxide and hydroxyl radicals mediate palmitate-induced cytotoxicity to hepatoma cells: relation to mitochondrial permeability transition. Free Radic Res 2007;41:38–49.
   PubMed Web of Science ®Google Scholar
• Nakamura S, Takamura T, Matsuzawa-Nagata N, Takayama H, Misu H, Noda H, et al. Palmitate induces insulin resistance in H4IIEC3 hepatocytes through reactive oxygen species produced by mitochondria. J Biol Chem 2009;284: 14809–14818.
   PubMed Web of Science ®Google Scholar
• Puri P, Baillie RA, Wiest MM, Mirshahi F, Choudhury J, Cheung O, et al. A lipidomic analysis of nonalcoholic fatty liver disease. Hepatology 2007; 46:1081–1090.
   PubMed Web of Science ®Google Scholar
• Caballero F, Fernández A, De Lacy AM, Fernández-Checa JC, Caballería J, García-Ruiz C. Enhanced free cholesterol, SREBP-2 and StAR expression in human NASH. J Hepatol 2009;50:789–796.
   PubMed Web of Science ®Google Scholar
• Anuka E, Gal M, Stocco DM, Orly J. Expression and roles of steroidogenic acute regulatory (StAR) protein in ‘non-classical’, extra-adrenal and extra-gonadal cells and tissues. Mol Cell Endocrinol 2013;371:47–61.
   Google Scholar
• Josekutty J, Iqbal J, Iwawaki T, Kohno K, Hussain MM. MTP inhibition induces ER stress and increases gene transcription via Ire1α/cJun to enhance plasma ALT/AST. J Biol Chem 2013; doi:10.1074/jbc.M113.459602.
   Google Scholar
• Van Rooyen DM, Gan LT, Yeh MM, Haigh WG, Larter CZ, Ioannou G, et al. Pharmacological cholesterol lowering reverses fibrotic NASH g in obese, diabetic mice with metabolic syndrome. J Hepatol 2013;59:144–152. doi:10.1016/ j.jhep.2013.02.024.
   PubMed Web of Science ®Google Scholar
• DeFronzo RA, Jacot E, Jequier E, Maeder E, Wahren J, Felber JP. The effect of insulin on the disposal of intravenous glucose. Results from indirect calorimetry and hepatic and femoral venous catheterization. Diabetes 1981;30: 1000–1007.
   PubMed Web of Science ®Google Scholar
• DeFronzo RA. Insulin secretion, insulin resistance, and obesity. Int J Obes 1982;6:73–82.
   Google Scholar
• Cheng Z, Tseng Y, White MF. Insulin signaling meets mitochondria in metabolism. Trends Endocrinol Metab 2010;21:589–598.
   PubMed Web of Science ®Google Scholar
• Rowland AF, Fazakerley DJ, James DE. Mapping insulin/GLUT4 circuitry. Traffic 2011;12:672–681.
   PubMedGoogle Scholar
• Fritsche L, Weigert C, Häring HU, Lehmann R. How insulin receptor substrate proteins regulate the metabolic capacity of the liver–implications for health and disease. Curr Med Chem 2008;15:1316–1329.
   PubMed Web of Science ®Google Scholar
• Aguirre V, Werner ED, Giraud J, Lee YH, Shoelson SE, White MF. Phosphorylation of Ser307 in insulin receptor substrate-1 blocks interactions with the insulin receptor and inhibits insulin action. J Biol Chem 2002;277:1531–1537.
   PubMed Web of Science ®Google Scholar
• Ichijo H, Nishida E, Irie K, ten Dijke P, Saitoh M, Moriguchi T, et al. Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways. Science 1997;275:90–94.
   PubMed Web of Science ®Google Scholar
• Lee YH, Giraud J, Davis RJ, White MF. c-Jun N-terminal kinase (JNK) mediates feedback inhibition of the insulin signaling cascade. J Biol Chem 2003;278:2896–2902.
   PubMed Web of Science ®Google Scholar
• Zhang L, Keung W, Samokhvalov V, Wang W, Lopaschuk GD. Role of fatty acid uptake and fatty acid beta-oxidation in mediating insulin resistance in heart and skeletal muscle. Biochim Biophys Acta 2010;1801:1–22.
   PubMed Web of Science ®Google Scholar
• Krssak M, Falk Petersen K, Dresner A, DiPietro L, Vogel SM, Rothman DL, et al. Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study. Diabetología 1999;42: 113–116.
   PubMed Web of Science ®Google Scholar
• Itani SI, Ruderman NB, Schmieder F, Boden G. Lipid- induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IkappaB-alpha. Diabetes 2002;51:2005–2011.
   PubMed Web of Science ®Google Scholar
• Ussher JR, Koves TR, Cadete VJ, Zhang L, Jaswal JS, Swyrd SJ, et al. Inhibition of de novo ceramide synthesis reverses diet-induced insulin resistance and enhances whole-body oxygen consumption. Diabetes 2010;59:2453–2464.
   PubMed Web of Science ®Google Scholar
• Holland WL, Brozinick JT, Wang LP, Hawkins ED, Sargent KM, Liu Y, et al. Inhibition of ceramide synthesis ameliorates glucocorticoid, saturated-fat, and obesity- induced insulin resistance. Cell Metab 2007;5:167–179.
   PubMed Web of Science ®Google Scholar
• Thompson AL, Cooney GJ. Acyl-CoA inhibition of hexokinase in rat and human skeletal muscle is a potential mechanism of lipid-induced insulin resistance. Diabetes 2000;49:1761–1765.
   Google Scholar
• Yu C, Chen Y, Cline GW, Zhang D, Zong H, Wang Y, et al. Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle. J Biol Chem 2002;277:50230–50236.
   PubMed Web of Science ®Google Scholar
• Kelly DP, Scarpulla RC. Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev 2004;18:357–368.
   PubMed Web of Science ®Google Scholar
• Murgia M, Giorgi C, Pinton P, Rizzuto R. Controlling metabolism and cell death: at the heart of mitochondrial calcium signalling. J Mol Cell Cardiol 2009;46:781–788.
   PubMed Web of Science ®Google Scholar
• Rimessi A, Giorgi C, Pinton P, Rizzuto R. The versatility of mitochondrial calcium signals: from stimulation of cell metabolism to induction of cell death. Biochim. Biophys Acta 2008;1777:808–816.
   PubMed Web of Science ®Google Scholar
• Lill R, Mühlenhoff U. Maturation of iron-sulfur proteins in eukaryotes: mechanisms, connected processes, and diseases. Ann Rev Biochem 2008;77:669–700.
   PubMed Web of Science ®Google Scholar
• Starkov AA. The role of mitochondria in reactive oxygen species metabolism and signaling. Ann N Y Acad Sci 2008; 1147:37–52.
   PubMed Web of Science ®Google Scholar
• Murphy MRP. How mitochondria produce reactive oxygen species. Biochem J 2009;417:1–13.
   PubMed Web of Science ®Google Scholar
• Kerner J, Parland WK, Minkler PE, Hoppel CL. Rat liver mitochondrial carnitine palmitoyltransferase-I, hepatic carnitine, and malonyl-CoA: effect of starvation. Arch Physiol Biochem 2008;114:161–170.
   PubMedGoogle Scholar
• Ussher JR, Lopaschuk GD. The malonyl CoA axis as a potential target for treating ischaemic heart disease. Cardiovas Res 2008;79:259–268.
   PubMed Web of Science ®Google Scholar
• Nyman LR, Cox KB, Hoopel CL, Kerner J, Barnoski BL, Hamm DA, et al. Homozygous carnitine palmitoyltransferase 1a (liver isoform) deficiency is lethal in the mouse. Mol Genet Metab 2005;86:179–187.
   PubMed Web of Science ®Google Scholar
• Ji S, You Y, Kerner J, Hoppel CL, Schoeb TR, Chick WS, et al. Homozygous carnitine palmitoyltransferase 1b (muscle isoform) deficiency is lethal in the mouse. Mol Genet Metab 2008;93:314–322.
   PubMed Web of Science ®Google Scholar
• Higgins AJ, Morville M, Burges RA, Blackburn KJ. Mechanism of action of oxfenicine on muscle metabolism. Biochim Biophys Res Commun 1981;100:291–296.
   PubMed Web of Science ®Google Scholar
• Koves TR, Ussher JR, Noland RC, Slentz D, Mosedale M, Ilkayeva O, et al. Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance. Cell Metab 2008;7:45–56.
   PubMed Web of Science ®Google Scholar
• Shulman GI, Rothman DL, Jue T, Stein P, DeFronzo RA, Shulman RG. Quantitation of muscle glycogen synthesis in normal subjects and subjects with non-insulin-dependent diabetes by 13C nuclear magnetic resonance spectroscopy. N Engl J Med 1990;322:223–228.
   PubMed Web of Science ®Google Scholar
• Randle PJ, Garland PB, Hales CN, Newsholme EA. The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1963;1:785–789.
   PubMed Web of Science ®Google Scholar
• Shulman GI. Cellular mechanisms of insulin resistance. J Clin Invest 2000;106:171–176.
   PubMed Web of Science ®Google Scholar
• Roden M, Price TB, Perseghin G, Petersen KF, Rothman DL, Cline GW, Shulman GI. Mechanism of free fatty acid- induced insulin resistance in humans. J Clin Invest 1996;97:2859–2865.
   PubMed Web of Science ®Google Scholar
• Griffin ME, Marcucci MJ, Cline GW, Bell K, Barucci N, Lee D, et al. Free fatty acid-induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signaling cascade. Diabetes 1999;48: 1270–1274.
   PubMed Web of Science ®Google Scholar
• Dresner A, Laurent D, Marcucci M, Griffin ME, Dufour S, Cline GW, et al. Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity. J Clin Invest 1999;103:253–259.
   PubMed Web of Science ®Google Scholar
• Timmers S, Nabben M, Bosma M, van Bree B, Lenaers E, van Beurden D, et al. Augmenting muscle diacylglycerol and triacylglycerol content by blocking fatty acid oxidation does not impede insulin sensitivity. Proc Natl Acad Sci USA 2012;109:11711–11716.
   PubMed Web of Science ®Google Scholar
• Begriche K, Massart J, Robin MA, Bonnet F, Fromenty B. Mitochondrial adaptations and dysfunctions in nonalcoholic fatty liver disease. Hepatology 2013; doi:10.1002/hep. 26226.
   Google Scholar
• Caldwell SH, Swerdlow RH, Khan EM, Iezzoni JC, Hespenheide EE, Parks JK, Parker WD Jr. Mitochondrial abnormalities in non-alcoholic steatohepatitis. J Hepatol 1999;31:430–434.
   PubMed Web of Science ®Google Scholar
• Sanyal AJ, Campbell-Sargent C, Mirshahi F, Rizzo WB, Contos MJ, Sterling RK, et al. Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology 2001;120:1183–1192.
   PubMed Web of Science ®Google Scholar
• Bowyer BA, Miles JM, Haymond MW, Fleming CR. L-carnitine therapy in home parenteral nutrition patients with abnormal liver tests and low plasma carnitine concentrations. Gastroenterology 1988;94:434–438.
   PubMed Web of Science ®Google Scholar
• Krähenbühl S, Mang G, Kupferschmidt H, Meier PJ, Krause M. Plasma and hepatic carnitine and coenzyme A pools in a patient with fatal, valproate induced hepatotoxicity. Gut 1995;37:140–143.
   PubMed Web of Science ®Google Scholar
• Harper P, Wadstrom C, Backman L, Cederblad G. Increased liver carnitine content in obese women. Am J Clin Nutri 1995;61:18–25.
   Google Scholar
• Garcia-Ruiz I, Rodríguez-Juan C, Díaz-Sanjuan T, del Hoyo P, Colina F, Muñoz-Yagüe T, Solís-Herruzo JA. Uric acid and anti-TNF antibody improve mitochondrial dysfunction in ob/ob mice. Hepatology 2006;44:581–591.
   PubMed Web of Science ®Google Scholar
• Serviddio G, Giudetti AM, Bellanti F, Priore P, Rollo T, Tamborra R, et al. Oxidation of hepatic carnitine palmitoyl transferase-I (CPT-I) impairs fatty acid beta-oxidation in rats fed a methionine-choline deficient diet. PLoS One 2011; 6:e24084.
   PubMed Web of Science ®Google Scholar
• Martin J, Maurhofer O, Bellance N, Benard G, Graber F, Hahn D, et al. Disruption of the histidine triad nucleotide-binding hint2 gene in mice affects glycemic control and mitochondrial function. Hepatology 2013;57:2037–2048.
   Google Scholar
• Rector RS, Morris EM, Ridenhour S, Meers GM, Hsu FF, Turk J, Ibdah JA. Selective hepatic insulin resistance in a murine model heterozygous for a mitochondrial trifunctional protein defect. Hepatology 2013; doi:10.1002/hep.26285.
   Google Scholar
• Liesa M, Shirihai OS. Mitochondrial dynamics in the regulation of nutrient utilization and energy expenditure. Cell Metab 2013;17:491–506.
   PubMed Web of Science ®Google Scholar
• Garcia-Roves P, Huss JM, Han DH, Hancock CR, Iglesias-Gutierrez E, Chen M, Holloszy JO. Raising plasma fatty acid concentration induces increased biogenesis of mitochondria in skeletal muscle. Proc Natl Acad Sci USA 2007;104:10709–10713.
   PubMed Web of Science ®Google Scholar
• Kelley DE, Goodpaster B, Wing RR, Simoneau JA. Skeletal muscle fatty acid metabolism in association with insulin resistance, obesity, and weight loss. Am J Physiol 1999;277:E1130–E1141.
   PubMed Web of Science ®Google Scholar
• Kelley DE, He J, Menshikova EV, Ritov VB. Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. Diabetes 2002;51:2944–2950.
   PubMed Web of Science ®Google Scholar
• Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, et al. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet 2003;34:267–273.
   PubMed Web of Science ®Google Scholar
• Patti ME, Butte AJ, Crunkhorn S, Cusi K, Berria R, Kashyap S, et al. Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes. Potential role of PGC1 and NRF1. Proc Natl Acad Sci 2003; 100:8466–8471.
   PubMed Web of Science ®Google Scholar
• Mogensen M, Sahlin K, Fernström M, Glintborg D, Vind BF, Beck-Nielsen H, Højlund K. Mitochondrial respiration is decreased in skeletal muscle of patients with type 2 diabetes. Diabetes 2007;56:1592–1599.
   PubMed Web of Science ®Google Scholar
• Phielix E, Schrauwen-Hinderling VB, Mensink M, Lenaers E, Meex R, Hoeks J, et al. Lower intrinsic ADP-stimulated mitochondrial respiration underlies in vivo mitochondrial dysfunction in muscle of male type 2 diabetic patients. Diabetes 2008;57:2943–2949.
   PubMed Web of Science ®Google Scholar
• Morino K, Petersen KF, Dufour S, Befroy D, Frattini J, Shatzkes N, et al. Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents. J Clin Invest 2005;115:3587–3593.
   PubMed Web of Science ®Google Scholar
• Ukropcova B, Sereda O, de Jonge L, Bogacka I, Nguyen T, Xie H, et al. Family history of diabetes links impaired substrate switching and reduced mitochondrial content in skeletal muscle. Diabetes 2007;56:720–727.
   PubMed Web of Science ®Google Scholar
• Petersen KF, Befroy D, Dufour S, Dziura J, Ariyan C, Rothman DL, et al. Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science 2003;300: 1140–1142.
   PubMed Web of Science ®Google Scholar
• Susin SA, Lorenzo HK, Zamzami N, Marzo I, Snow BE, Brothers GM, et al. Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 1999;397:441–446.
   PubMed Web of Science ®Google Scholar
• Wissing S, Ludovico P, Herker E, Buttner S, Engelhardt SM, Decker T, et al. An AIF orthologue regulates apoptosis in yeast. J Cell Biol 2004;166:969–974.
   PubMed Web of Science ®Google Scholar
• Cheung EC, Joza N, Steenaart NA, McClellan KA, Neuspiel M, McNamara S, et al. Dissociating the dual roles of apoptosis-inducing factor in maintaining mitochondrial structure and apoptosis. EMBO J 2006;25:4061–4073.
   PubMed Web of Science ®Google Scholar
• Joza N, Oudit GY, Brown D, Benit P, Kassiri Z, Vahsen N, et al. Muscle-specific loss of apoptosis-inducing factor leads to mitochondrial dysfunction, skeletal muscle atrophy, and dilated cardiomyopathy. Mol Cell Biol 2005;25:10261–10272.
   PubMedGoogle Scholar
• Vahsen N, Cande C, Briere JJ, Benit P, Joza N, Larochette N, et al. AIF deficiency compromises oxidative phosphorylation. EMBO J 2004;23:4679–4689.
   PubMed Web of Science ®Google Scholar
• Pospisilik JA, Knauf C, Joza N, Benit P, Orthofer M, Cani PD, et al. Targeted deletion of AIF decreases mitochondrial oxidative phosphorylation and protects from obesity and diabetes. Cell 2007;131:476–491.
   PubMed Web of Science ®Google Scholar
• Gaspari M, Larsson NG, Gustafsson CM. The transcription machinery in mammalian mitochondria. Biochim Biophys Acta 2004;1659:148–152.
   PubMedGoogle Scholar
• Larsson NG, Wang J, Wilhelmsson H, Oldfors A, Rustin P, Lewandoski M, et al. Mitochondrial transcription factor A is necessary for mtDNA maintenance and embryogenesis in mice. Nat Genet 1998;18:231–236.
   PubMed Web of Science ®Google Scholar
• Wredenberg A, Wibom R, Wilhelmsson H, Graff C, Wiener HH, Burden SJ, et al. Increased mitochondrial mass in mitochondrial myopathy mice. Proc Natl Acad Sci 2002; 99:15066–15071.
   PubMed Web of Science ®Google Scholar
• Wredenberg A, Freyer C, Sandström ME, Katz A, Wibom R, Westerblad H, Larsson NG. Respiratory chain dysfunction in skeletal muscle does not cause insulin resistance. Biochem Biophys Res Commun 2006;350:202–207.
   PubMed Web of Science ®Google Scholar
• Vernochet C, Mourier A, Bezy O, Macotela Y, Boucher J, Rardin MJ, et al. Adipose-specific deletion of TFAM increases mitochondrial oxidation and protects mice against obesity and insulin resistance. Cell Metab 2012;16: 765–776.
   PubMed Web of Science ®Google Scholar
• Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J Clin Invest 2005;115:1111–1119.
   PubMed Web of Science ®Google Scholar
• Hancock CR, Han DH, Chen M, Terada S, Yasuda T, Wright DC, Holloszy JO. High-fat diets cause insulin resistance despite an increase in muscle mitochondria. Proc Natl Acad Sci 2008;105:7815–7820.
   PubMed Web of Science ®Google Scholar
• Turner N, Bruce CR, Beale SM, Hoehn KL, So T, Rolph MS, Cooney GJ. Excess lipid availability increases mitochondrial fatty acid oxidative capacity in muscle: evidence against a role for reduced fatty acid oxidation in lipid-induced insulin resistance in rodents. Diabetes 2007;56:2085–2092.
   PubMed Web of Science ®Google Scholar
• Stephens TW, Higgins AJ, Cook GA, Harris RA. Two mechanisms produce tissue-specific inhibition of fatty acid oxidation by oxfenicine. Biochem J 1985;227: 651–660.
   PubMed Web of Science ®Google Scholar
• Wen CP, Wai JP, Tsai MK, Yang YC, Cheng TY, Lee MC, et al. Minimum Amount of physical activity for reduced mortality and extended life expectancy: a prospective cohort study. Lancet.2011;1378:1244–53.
   Google Scholar
• Orozco LJ, Buchleitner AM, Gimenez-Perez G, Roqué I, Figuls M, Richter B, et al. Exercise or exercise and diet for preventing type 2 diabetes mellitus. Cochrane Database Syst Rev 2008;3:CD003054. doi:10.02/1461051858.
   Google Scholar
• Fisher-Wellman K, Bloomer RJ. Acute exercise and oxidative stress: a 30 year history. Dyn Med 2009;8:1.
   PubMedGoogle Scholar
• Schulz TJ, Zarse K, Voigt A, Urban N, Birringer M, Ristow M. Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress. Cell Metab 2007;6:280–93.
   PubMed Web of Science ®Google Scholar
• Peternelj TT, Coombes JS. Antioxidant supplementation during exersice training: beneficial or detrimental?Sports Med 2011;41:1043–1069.
   PubMed Web of Science ®Google Scholar
• Yfanti C, Nielsen AR, Akerström T, Nielsen S, Rose AJ, Richter EA, et al. Effect of antioxidant supplementation on insulin sensitivity in response to endurance exercise training. Am J Physiol Endocrinol Metab 2011;300:E761–E770.
   Google Scholar
• Praet SF, Van Loon LJ. Exercice therapy in Type 2 diabetes. Acta Diabetol 2009;46:263–278.
   PubMed Web of Science ®Google Scholar
• Stephens JW, Khanolkar MP, Bain SC. The biological relevance and measurement of oxidative stress in diabetes and CVD. Atherosclerosis 2009;202:321–329.
   PubMed Web of Science ®Google Scholar
• Vial G, Dubouchaud H, Couturier K, Cottet-Rousselle C, Taleux N, Athias A, et al. Effects of a high-fat diet on energy metabolism and ROS production in rat liver. J Hepatol 2011;54:348–356.
   PubMed Web of Science ®Google Scholar
• Li J, Romestaing C, Han X, Li Y, Hao X, Wu Y, et al. Cardiolipin remodeling by ALCAT1 links oxidative stress and mitochondrial dysfunction to obesity. Cell Metab 2010; 12:154–165.
   PubMedGoogle Scholar
• Aoun M, Feillet-Coudray C, Fouret G, Chabi B, Crouzier D, Ferreri C, et al. Rat liver mitochondrial membrane characteristics and mitochondrial functions are more profoundly altered by dietary lipid quantity than by dietary lipid quality: effect of different nutritional lipid patterns. Br J Nutr 2011;20:1–13.
   Google Scholar
• Loh K, Deng H, Fukushima A, Cai X, Boivin B, Galic S, et al. Reactive oxygen species enhance insulin sensitivity. Cell Metab 2009;10:260–272.
   PubMed Web of Science ®Google Scholar
• Hoehn KL, Salmon AB, Hohnen-Behrens C, Turner N, Hoy AJ, Maghzal GJ. Insulin resistance is a cellular antioxidant defense mechanism. Proc Natl Acad Sci USA 2009; 106:17787–17792.
   PubMed Web of Science ®Google Scholar
• Elchebly M, Payette P, Michaliszyn E, Cromlish W, Collins S, Loy AL, et al. Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene. Science 1999;283:1544–1548.
   PubMed Web of Science ®Google Scholar
• Iwakami S, Misu H, Takeda T, Sugimori M, Matsugo S, Kaneko S, Takamura T. Concentration-dependent dual effects of hydrogen peroxide on insulin signal transduction in H4IIEC hepatocytes. PLoS One 2011;6:e27401.
   PubMed Web of Science ®Google Scholar
• Kamata H, Honda S, Maeda S, Chang L, Hirata H, Karin M. Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases. Cell 2005;120:649–61.
   PubMed Web of Science ®Google Scholar
• Anderson EJ, Lustig ME, Boyle KE, Woodlief TL, Kane DA, Lin CT, et al. Mitochondrial H202 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans. J Clin Invest 2009;119:573–581.
   PubMed Web of Science ®Google Scholar
• Daiber A. Redox signaling from mitochondria involves mitochondrial pores and reactive oxygen species. Biochim Biophys Acta 2010;1797:897–906.
   PubMed Web of Science ®Google Scholar
• von Montfort C, Matias N, Fernandez A, Fucho R, Conde de la Rosa L, Martinez-Chantar ML, et al. Mitochondrial GSH determines the toxic or therapeutic potential of superoxide scavenging in steatohepatitis. J Hepatol 2012; 57:852–859.
   PubMed Web of Science ®Google Scholar
• Laurent A, Nicco C, Tran Van Nhieu J, Borderie D, Chéreau C, Conti F, et al. Pivotal role of superoxide anion and beneficial effect of antioxidant molecules in murine steatohepatitis. Hepatology 2004;39:1277–1285.
   PubMed Web of Science ®Google Scholar
• Perlemuter G, Davit-Spraul A, Cosson C, Conti M, Bigorgne A, Paradis V, et al. Increase in liver antioxidant enzyme activities in non- alcoholic fatty liver disease. Liver Int 2005;25:946–953.
   PubMed Web of Science ®Google Scholar
• Marí M, Morales A, Colell A, García-Ruiz C, Fernández-Checa JC. Mitochondrial GSH, a key survival antioxidant. Antiox Red Signal 2009;11:2685–700.
   PubMed Web of Science ®Google Scholar
• Salvemini D, Riley DP, Cuzzocrea S. SOD mimetics are coming of age. Nat Rev Drug Discov 2002;1:367–374.
   PubMed Web of Science ®Google Scholar
• Garcia-Ruiz C, Marí M, Colell A, Morales A, Fernandez-Checa JC. Metabolic therapy: lessons from liver diseases. Curr Pharm Dis 2011;17:3933–3944.
   Google Scholar
• Garcia-Ruiz C, Kaplowitz N, Fernandez-Checa JC. Role of mitochondria in alcoholic liver disease. Curr Pathobiol Report 2013;159–168.
   Google Scholar
• Brunmair B, Staniek K, Gras F, Scharf N, Althaym A, Clara R, et al. Thiazolidinediones, like metformin, inhibit respiratory complex I: a common mechanism contributing to their antidiabetic actions?Diabetes 2004;53:1052–1059.
   PubMed Web of Science ®Google Scholar
• Lin HZ, Yang SQ, Chuckaree C, Kuhajda F, Ronnet G, Diehl AM. Metformin reverses fatty liver disease in obese, leptin-deficient mice. Nat Med 2000;6:998–1003.
   PubMed Web of Science ®Google Scholar
• Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. New England J Med 2010;362:1675–1685.
   PubMed Web of Science ®Google Scholar