• 1
    Dianzani MU. The content of adenosine polyphosphates in fatty livers. Biochem J 1957; 65: 116124.
  • 2
    Pessayre D, Fromenty B. NASH: a mitochondrial disease. J Hepatol 2005; 42: 928940.
  • 3
    Cortez-Pinto H, Chatham J, Chacko VP, Arnold C, Rashid A, Diehl AM. Alterations in liver ATP homeostasis in human nonalcoholic steatohepatitis: a pilot study. JAMA 1999; 282: 16591664.
  • 4
    Perez-Carrera M, Del Hoyo P, Martin MA, Rubio JC, Martin A, Castellano G, et al. Defective hepatic mitochondrial respiratory chain in patients with nonalcoholic steatohepatitis. HEPATOLOGY 2003; 38: 9991007.
  • 5
    Baffy G. Uncoupling protein-2 and non-alcoholic fatty liver disease. Front Biosci 2005; 10: 20822096.
  • 6
    Sternlieb I, Berger JE. Optical diffraction studies of crystalline structures in electron micrographs. J Cell Biol 1969; 43: 448455.
  • 7
    Caldwell SH, Swerdlow RH, Khan EM, Iezzoni JC, Hespenheide EE, Parks JK, et al. Mitochondrial abnormalities in non-alcoholic steatohepatitis. J Hepatol 1999; 31: 430434.
  • 8
    Chedid A, Mendenhall CL, Tosch T, Chen T, Rabin L, Garcia-Pont P, et al. Significance of megamitochondria in alcoholic liver disease. Gastroenterology 1986; 90: 18581864.
  • 9
    Caldwell SH, Chang CY, Nakamoto RK, Krugner-Higby, L. Mitochondria in nonalcoholic fatty liver disease. Clin Liver Dis 2004; 8: 595617.
  • 10
    Sanyal AJ, Campbell-Sargent C, Mirshani F, Rizzo WB, Contos MJ, Sterling RK, et al. Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology 2001; 120: 11831192.
  • 11
    Le TH, Caldwell SH, Redick JA, Sheppard BL, Davis CA, Arseneau K, et al. The lobular distribution of mitochondrial abnormalities in NASH. HEPATOLOGY 2004; 39: 14231429.
  • 12
    Fajas L, Auboeuf D, Raspe E, Schoonjans K, Lefebvre A-M, Saladin R, et al. The organization, promoter analysis, and expression of the human PPAR-γ gene. J Biol Chem 1997; 272: 1877918789.
  • 13
    Law RE, Goetze S, Xi X-P, Jackson S, Kawano Y, Demer L, et al. Expression and function of PPARγ in rat and human vascular smooth muscle cells. Circulation 2000; 101: 13111318.
  • 14
    Roberts AW, Thomas A, Rees A, Evans M. Peroxisome proliferator-activated receptor-gamma agonists in atherosclerosis: current evidence and future directions. Curr Opin Lipidol 2003; 14: 567573.
  • 15
    Caldwell SH, Argo CK, Al-Osaimi AM. Therapy of NAFLD: insulin sensitizing agents. J Clin Gastroenterol 2006; 40(Suppl 1): S61S66.
  • 16
    Belfort R, Harrison SA, Brown K, Darland C, Finch J, Hardies J, et al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med 2006; 355: 22972307.
  • 17
    McCullough AJ. Thiazolidinediones for nonalcoholic steatohepatitis—promising but not ready for prime time. N Engl J Med 2006; 355: 23612363.
  • 18
    Tiikkainen M, Hakkinen A-M, Korsheninnikova E, Nyman T, Makimattila S, Yki-Jarvinen H. Effects of rosiglitazone and metformin on liver fat content, hepatic insulin resistance, insulin clearance, and gene expression in adipose tissue in patients with type 2 diabetes. Diabetes 2004; 53: 21692176.
  • 19
    Shadid S, Jensen MD. Effects of pioglitazone versus diet and exercise on metabolic health and fat distribution in upper body obesity. Diabetes Care 2003; 26: 31483152.
  • 20
    Wilson-Fritch L, Nicoloro S, Chouinard M, Lazar MA, Chui PC, Leszyk J, et al. Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone. J Clin Invest 2004; 114: 12811289.
  • 21
    Laplante M, Festuccia WT, Soucy G, Gelinas Y, Lalonde J, Berger JP, et al. Mechanisms of the depot specificity of peroxisome proliferator-activated receptor γ action on adipose tissue metabolism. Diabetes 2006; 55: 27712778.
  • 22
    Neuschwander-Tetri BA, Brunt EM, Wehmeier KR, Oliver D, Bacon BR. Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR-γ ligand rosiglitazone. HEPATOLOGY 2003; 38: 10081017.
  • 23
    Arias IM. The hepatocyte organization. In: AriasIM, JacobyWB, PopperH, SchachterD, ShafritzDA, eds. The Liver: Biology and Pathobiology. 2nd ed. New York, NY: Raven Press; 1988: 9.
  • 24
    Ikura Y, Ohsawa M, Suekane T, Fukushima H, Itabe H, Jomura H, et al. Localization of oxidized phosphatidylcholine in nonalcoholic fatty liver disease: impact on disease progression. HEPATOLOGY 2006; 43: 506514.
  • 25
    Caldwell SH, Redick JA, Chang CY, Davis CA, Argo CK, Al Osaimi AM. Enlarged hepatocytes in NAFLD examined with osmium fixation: does microsteatosis underlie cellular ballooning in NASH? Am J Gastroenterol 2006; 101: 16771678.
    Direct Link:
  • 26
    Feldstein AE, Canby A, Angulo P, Taniai M, Burgart LJ, Lindor KD, et al. Hepatocyte apoptosis and FAS expression are prominent features of human nonalcoholic steatohepatitis. Gastroenterology 2003; 125: 437443.
  • 27
    Rashid A, Wu T-C, Huang C-C, Chen C-H, Lin HZ, Yang SQ, et al. Mitochondrial proteins that regulate apoptosis and necrosis are induced in mouse fatty liver. HEPATOLOGY 1999; 29: 11311138.
  • 28
    Caldwell SH, Hespenheide EE, Redick JA, Iezzoni JC, Battle EH, Sheppard BL. A pilot study of a thiazolidinedione, troglitazone, in nonalcoholic steatohepatitis. Am J Gastroenterol 2001; 96: 519525.
    Direct Link:
  • 29
    Oliveira CP, Coelho AM, Barbeiro HV, Lima VM, Soriano F, Ribeiro C, et al. Liver mitochondrial dysfunction and oxidative stress in the pathogenesis of experimental nonalcoholic fatty liver disease. Braz J Med Biol Res 2006; 39: 189194.
  • 30
    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: 10521059.
  • 31
    Van Huyen JP, Batisse D, Heudes D, Belair MF, Piketty C, Gonzalez-Canali G, et al. Alteration of cytochrome oxidase subunit I labeling is associated with severe mitochondriopathy in NRTI-related hepatotoxicity in HIV patients. Mod Pathol 2006; 19: 12771288.
  • 32
    Smith SR, De Jonge L, Volaufova J, Li Y, Xie H, Bray GA. Effect of pioglitazone on body composition and energy expenditure: a randomized controlled trial. Metabolism 2005; 54: 2432.
  • 33
    Laplante M, Festuccia WT, Soucy G, Gelinas Y, Lalonde J, Berger JP, et al. Mechanisms of the depot specificity of peroxisome proliferator-activated receptor gamma action on adipose tissue metabolism. Diabetes 2006; 55: 27712778.
  • 34
    Bogacka I, Ukropcova B, McNeil M, Gimble JM, Smith SR. Structural and functional consequences of mitochondrial biogenesis in human adipocytes in vivo. J Clin Endocrinol Metab 2005; 90: 66506656.
  • 35
    Bogacka I, Xie H, Bray GA, Smith SR. Pioglitazone induces mitochondrial biogenesis in human subcutaneous adipose tissue in vivo. Diabetes 2005; 54: 13921399.
  • 36
    LeBrasseur NK, Kelly M, Tsao TS, Farmer SR, Saha AK, Ruderman NB, et al. Thiazolidinediones can rapidly activate AMP-activated protein kinase in mammalian tissues. Am J Physiol Endocrinol Metab 2006; 291: E175E181.
  • 37
    Saha AK, Avilucea PR, Ye JM, Assifi MM, Kraegen EW, Ruderman NB. Pioglitazone treatment activates AMP-activated protein kinase in rat liver and adipose tissue in vivo. Biochem Biophys Res Commun 2004; 314: 580585.
  • 38
    Lutchman G, Promrat K, Kleiner DE, Heller T, Ghany MG, Yanovski JA, et al. Changes in serum adipokine levels during pioglitazone treatment for nonalcoholic steatohepatitis: relationship to histological improvement. Clin Gastroenterol Hepatol 2006; 4: 10481052.
  • 39
    Wilson-Fritch L, Nicoloro S, Chouinard M, Lazar MA, Chui PC, Leszyk J, et al. Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone. J Clin Invest 2004; 114: 12811299.
  • 40
    Chavin KD, Yang S, Lin HZ, Chatham J, Chacko VP, Hoek JB, et al. Obesity induces expression of uncoupling protein-2 in hepatocytes and promotes liver ATP depletion. J Biol Chem 1999; 274: 56925700.
  • 41
    Schadinger SE, Bucher NL, Schreiber BM, Farmer SR. PPARgamma2 regulates lipogenesis and lipid accumulation in steatotic hepatocytes. Am J Physiol Endocrinol Metab 2005; 288: E1195E1205.