Nonalcoholic fatty liver disease and mitochondrial dysfunction.

Nonalcoholic fatty liver disease (NAFLD) includes hepatic steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. NAFLD is the most common liver disorder in the United States and worldwide. Due to the rapid rise of the metabolic syndrome, the prevalence of NAFLD has recently dramatically increased and will continue to increase. NAFLD has also the potential to progress to hepatocellular carcinoma (HCC) or liver failure. NAFLD is strongly linked to caloric overconsumption, physical inactivity, insulin resistance and genetic factors. Although significant progress in understanding the pathogenesis of NAFLD has been achieved in years, the primary metabolic abnormalities leading to lipid accumulation within hepatocytes has remained poorly understood. Mitochondria are critical metabolic organelles serving as "cellular power plants". Accumulating evidence indicate that hepatic mitochondrial dysfunction is crucial to the pathogenesis of NAFLD. This review is focused on the significant role of mitochondria in the development of NAFLD.

[1]  E. Clementi,et al.  TNF-alpha downregulates eNOS expression and mitochondrial biogenesis in fat and muscle of obese rodents. , 2006, The Journal of clinical investigation.

[2]  F. Colina,et al.  Uric acid and anti‐TNF antibody improve mitochondrial dysfunction in ob/ob mice , 2006, Hepatology.

[3]  H. Cortez‐Pinto,et al.  Non-alcoholic steatohepatitis and metabolic syndrome , 2006, Current opinion in clinical nutrition and metabolic care.

[4]  M. Osman,et al.  Invasive and non-invasive investigations for tamoxifen-induced non-alcoholic steatohepatitis (NASH): the benefit of computed tomography scan guided liver biopsy. , 2006, Pathology.

[5]  D. Kelly,et al.  PGC-1 coactivators: inducible regulators of energy metabolism in health and disease. , 2006, The Journal of clinical investigation.

[6]  C. Corless,et al.  The metabolic syndrome resulting from a knockout of the NEIL1 DNA glycosylase. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[7]  D. Pessayre,et al.  Mitochondrial dysfunction in NASH: causes, consequences and possible means to prevent it. , 2006, Mitochondrion.

[8]  B. Neuschwander‐Tetri Nonalcoholic steatohepatitis and the metabolic syndrome. , 2005, The American journal of the medical sciences.

[9]  S. Sanderson,et al.  The natural history of nonalcoholic fatty liver disease: a population-based cohort study. , 2005, Gastroenterology.

[10]  G. Bray,et al.  A high-fat diet coordinately downregulates genes required for mitochondrial oxidative phosphorylation in skeletal muscle. , 2005, Diabetes.

[11]  D. Pessayre,et al.  NASH: a mitochondrial disease. , 2005, Journal of hepatology.

[12]  Christoph Handschin,et al.  Metabolic control through the PGC-1 family of transcription coactivators. , 2005, Cell metabolism.

[13]  O. Cummings,et al.  Design and validation of a histological scoring system for nonalcoholic fatty liver disease , 2005, Hepatology.

[14]  A. Lonardo,et al.  Should Nonalcoholic Fatty Liver Disease Be Renamed? , 2005, Digestive Diseases.

[15]  J. Cline,et al.  Mice heterozygous for a defect in mitochondrial trifunctional protein develop hepatic steatosis and insulin resistance. , 2005, Gastroenterology.

[16]  Z. Goodman,et al.  Predictors of Nonalcoholic Steatohepatitis and Advanced Fibrosis in Morbidly Obese Patients , 2005, Obesity surgery.

[17]  Yoshimasa Kusano,et al.  Prevalence of fatty liver in Japanese children and relationship to obesity , 1995, Digestive Diseases and Sciences.

[18]  Jonathan C. Cohen,et al.  Prevalence of hepatic steatosis in an urban population in the United States: Impact of ethnicity , 2004, Hepatology.

[19]  M. Lazar,et al.  Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone. , 2004, The Journal of clinical investigation.

[20]  J. Reddy,et al.  PPARα in the pathogenesis of fatty liver disease , 2004 .

[21]  M. Rao,et al.  PPARalpha in the pathogenesis of fatty liver disease. , 2004, Hepatology.

[22]  Jiandie D. Lin,et al.  Defects in Adaptive Energy Metabolism with CNS-Linked Hyperactivity in PGC-1α Null Mice , 2004, Cell.

[23]  J. Horton,et al.  Molecular mediators of hepatic steatosis and liver injury. , 2004, The Journal of clinical investigation.

[24]  F. Brunetti,et al.  Liver Involvement in Obese Children (Ultrasonography and Liver Enzyme Levels at Diagnosis and During Follow-up in an Italian Population) , 1997, Digestive Diseases and Sciences.

[25]  L. Tartaglia,et al.  Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. , 2003, The Journal of clinical investigation.

[26]  Y. Kamei,et al.  PPARγ coactivator 1β/ERR ligand 1 is an ERR protein ligand, whose expression induces a high-energy expenditure and antagonizes obesity , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[27]  J. Arenas,et al.  Defective hepatic mitochondrial respiratory chain in patients with nonalcoholic steatohepatitis , 2003, Hepatology.

[28]  Jiandie D. Lin,et al.  PGC-1β in the Regulation of Hepatic Glucose and Energy Metabolism* , 2003, Journal of Biological Chemistry.

[29]  C. McClain,et al.  Cytokines and NASH: A pilot study of the effects of lifestyle modification and vitamin E , 2003, Hepatology.

[30]  Jiandie D. Lin,et al.  Bioenergetic Analysis of Peroxisome Proliferator-activated Receptor γ Coactivators 1α and 1β (PGC-1α and PGC-1β) in Muscle Cells* , 2003, Journal of Biological Chemistry.

[31]  M. Daly,et al.  PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes , 2003, Nature Genetics.

[32]  A. Butte,et al.  Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1 , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[33]  R. Evans,et al.  Peroxisome-Proliferator-Activated Receptor δ Activates Fat Metabolism to Prevent Obesity , 2003, Cell.

[34]  Shelly C. Lu,et al.  Functional proteomics of nonalcoholic steatohepatitis: Mitochondrial proteins as targets of S-adenosylmethionine , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[35]  R. Evans,et al.  Peroxisome-proliferator-activated receptor delta activates fat metabolism to prevent obesity. , 2003, Cell.

[36]  Y. Kamei,et al.  PPARgamma coactivator 1beta/ERR ligand 1 is an ERR protein ligand, whose expression induces a high-energy expenditure and antagonizes obesity. , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[37]  Jiandie D. Lin,et al.  Bioenergetic analysis of peroxisome proliferator-activated receptor gamma coactivators 1alpha and 1beta (PGC-1alpha and PGC-1beta) in muscle cells. , 2003, The Journal of biological chemistry.

[38]  Jiandie D. Lin,et al.  PGC-1beta in the regulation of hepatic glucose and energy metabolism. , 2003, The Journal of biological chemistry.

[39]  D. Lebensztejn,et al.  Ultrastructure of hepatocyte mitochondria in nonalcoholic steatohepatitis in pediatric patients: usefulness of electron microscopy in the diagnosis of the disease , 2003, American Journal of Gastroenterology.

[40]  D. Pessayre,et al.  Impaired adaptive resynthesis and prolonged depletion of hepatic mitochondrial DNA after repeated alcohol binges in mice. , 2002, Gastroenterology.

[41]  Jiandie D. Lin,et al.  Transcriptional co-activator PGC-1α drives the formation of slow-twitch muscle fibres , 2002, Nature.

[42]  A. Häkkinen,et al.  Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum free fatty acids independent of obesity in normal men. , 2002, The Journal of clinical endocrinology and metabolism.

[43]  V. Giguère To ERR in the estrogen pathway , 2002, Trends in Endocrinology & Metabolism.

[44]  Jiandie D. Lin,et al.  Peroxisome Proliferator-activated Receptor γ Coactivator 1β (PGC-1β), A Novel PGC-1-related Transcription Coactivator Associated with Host Cell Factor* , 2002, The Journal of Biological Chemistry.

[45]  Jiandie D. Lin,et al.  Peroxisome proliferator-activated receptor gamma coactivator 1beta (PGC-1beta ), a novel PGC-1-related transcription coactivator associated with host cell factor. , 2002, The Journal of biological chemistry.

[46]  Jiandie D. Lin,et al.  Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres. , 2002, Nature.

[47]  J. Crespo,et al.  Gene expression of tumor necrosis factor α and TNF‐receptors, p55 and p75, in nonalcoholic steatohepatitis patients , 2001 .

[48]  Marc Montminy,et al.  CREB regulates hepatic gluconeogenesis through the coactivator PGC-1 , 2001, Nature.

[49]  Guillaume Adelmant,et al.  Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1 , 2001, Nature.

[50]  P. D. James,et al.  Findings on liver biopsy to investigate abnormal liver function tests in the absence of diagnostic serology. , 2001, Journal of hepatology.

[51]  J. Ibdah,et al.  Lack of mitochondrial trifunctional protein in mice causes neonatal hypoglycemia and sudden death. , 2001, The Journal of clinical investigation.

[52]  J. Clore,et al.  Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. , 2001, Gastroenterology.

[53]  T. Hashimoto,et al.  PEROXISOMAL β-OXIDATION AND PEROXISOME PROLIFERATOR–ACTIVATED RECEPTOR α: An Adaptive Metabolic System , 2001 .

[54]  T Hashimoto,et al.  Peroxisomal beta-oxidation and peroxisome proliferator-activated receptor alpha: an adaptive metabolic system. , 2001, Annual review of nutrition.

[55]  Miguel Ángel Martínez,et al.  Tumor Necrosis Factor-α Increases the Steady-state Reduction of Cytochrome b of the Mitochondrial Respiratory Chain in Metabolically Inhibited L929 Cells* , 2000, The Journal of Biological Chemistry.

[56]  K. Hensley,et al.  Dietary choline restriction causes complex I dysfunction and increased H(2)O(2) generation in liver mitochondria. , 2000, Carcinogenesis.

[57]  J. Parks,et al.  Mitochondrial abnormalities in non-alcoholic steatohepatitis. , 1999, Journal of hepatology.

[58]  B. Neuschwander‐Tetri,et al.  Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions , 1999, American Journal of Gastroenterology.

[59]  V. Mootha,et al.  Mechanisms Controlling Mitochondrial Biogenesis and Respiration through the Thermogenic Coactivator PGC-1 , 1999, Cell.

[60]  H. Cortez‐Pinto,et al.  Lipids up-regulate uncoupling protein 2 expression in rat hepatocytes. , 1999, Gastroenterology.

[61]  E. Yeh,et al.  Inhibition of mitochondrial respiratory chain complex I by TNF results in cytochrome c release, membrane permeability transition, and apoptosis , 1998, Oncogene.

[62]  C. Day,et al.  Steatohepatitis: a tale of two "hits"? , 1998, Gastroenterology.

[63]  D. Pessayre,et al.  Steatohepatitis-inducing drugs cause mitochondrial dysfunction and lipid peroxidation in rat hepatocytes. , 1998, Gastroenterology.

[64]  K. Umesono,et al.  The nuclear receptor superfamily: The second decade , 1995, Cell.

[65]  N. Kaplowitz,et al.  Role of oxidative stress generated from the mitochondrial electron transport chain and mitochondrial glutathione status in loss of mitochondrial function and activation of transcription factor nuclear factor-kappa B: studies with isolated mitochondria and rat hepatocytes. , 1995, Molecular pharmacology.

[66]  D. Pessayre,et al.  Inhibition of mitochondrial beta-oxidation as a mechanism of hepatotoxicity. , 1995, Pharmacology & therapeutics.

[67]  F. Schaffner,et al.  Nonalcoholic fatty liver disease. , 1986, Progress in liver diseases.