Hepatic molecular effects of rosiglitazone in human non‐alcoholic steatohepatitis suggest long‐term pro‐inflammatory damage

Glitazones are agonists of peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) and have been proposed for the treatment of non‐alcoholic steatohepatitis (NASH). However, efficacy results are conflicting and hepatic molecular changes induced by glitazones are mostly unknown. The aim of this study was to analyze the hepatic inflammatory and fibrogenic molecular effects of rosiglitazone in NASH patients.

[1]  R. Loomba,et al.  Meta‐analysis: pioglitazone improves liver histology and fibrosis in patients with non‐alcoholic steatohepatitis , 2012, Alimentary pharmacology & therapeutics.

[2]  A. Webster,et al.  The role of thiazolidinediones in non-alcoholic steatohepatitis - a systematic review and meta analysis. , 2011, Journal of hepatology.

[3]  Christopher D. Williams,et al.  Rosiglitazone versus rosiglitazone and metformin versus rosiglitazone and losartan in the treatment of nonalcoholic steatohepatitis in humans: A 12‐month randomized, prospective, open‐ label trial , 2011, Hepatology.

[4]  Nancy Claude,et al.  Comparative Gene Expression Profiles Induced by PPARγ and PPARα/γ Agonists in Human Hepatocytes , 2011, PloS one.

[5]  B. Neuschwander‐Tetri,et al.  Therapeutic trials in nonalcoholic steatohepatitis: Insulin sensitizers and related methodological issues , 2010, Hepatology.

[6]  Stephen T. C. Wong,et al.  Rosiglitazone attenuates age‐ and diet‐associated nonalcoholic steatohepatitis in male low‐density lipoprotein receptor knockout mice , 2010, Hepatology.

[7]  G. Musso,et al.  A meta‐analysis of randomized trials for the treatment of nonalcoholic fatty liver disease , 2010, Hepatology.

[8]  Vincent Wai-Sun Wong,et al.  Disease progression of non-alcoholic fatty liver disease: a prospective study with paired liver biopsies at 3 years , 2010, Gut.

[9]  B. Neuschwander‐Tetri,et al.  Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. , 2010, The New England journal of medicine.

[10]  P. Giral,et al.  Long‐term efficacy of rosiglitazone in nonalcoholic steatohepatitis: Results of the fatty liver improvement by rosiglitazone therapy (FLIRT 2) extension trial , 2009, Hepatology.

[11]  M. Lemoine,et al.  Definition and natural history of metabolic steatosis: clinical aspects of NAFLD, NASH and cirrhosis. , 2008, Diabetes & metabolism.

[12]  Philippe Giral,et al.  Rosiglitazone for nonalcoholic steatohepatitis: one-year results of the randomized placebo-controlled Fatty Liver Improvement with Rosiglitazone Therapy (FLIRT) Trial. , 2008, Gastroenterology.

[13]  J. Solís-Herruzo,et al.  Effects of rosiglitazone on the liver histology and mitochondrial function in ob/ob mice , 2007, Hepatology.

[14]  J. Hardies,et al.  A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. , 2006, The New England journal of medicine.

[15]  G. Schroth,et al.  Differences in hepatotoxicity and gene expression profiles by anti-diabetic PPAR γ agonists on rat primary hepatocytes and human HepG2 cells , 2006, Molecular Diversity.

[16]  Béatrice Desvergne,et al.  From molecular action to physiological outputs: peroxisome proliferator-activated receptors are nuclear receptors at the crossroads of key cellular functions. , 2006, Progress in lipid research.

[17]  J. Capeau,et al.  Altered hepatic expression of SREBP-1 and PPARγ is associated with liver injury in insulin-resistant lipodystrophic HIV-infected patients , 2006, AIDS.

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

[19]  J. Auwerx,et al.  Impaired expression of the peroxisome proliferator-activated receptor alpha during hepatitis C virus infection. , 2005, Gastroenterology.

[20]  R. Rippe,et al.  Peroxisome Proliferator-activated Receptor γ Induces a Phenotypic Switch from Activated to Quiescent Hepatic Stellate Cells* , 2004, Journal of Biological Chemistry.

[21]  D. Matthews,et al.  The assessment of insulin resistance in man , 2002, Diabetic medicine : a journal of the British Diabetic Association.

[22]  D. Crabb,et al.  Antidiabetic thiazolidinediones inhibit collagen synthesis and hepatic stellate cell activation in vivo and in vitro. , 2002, Gastroenterology.

[23]  N. Enomoto,et al.  Pioglitazone prevents early-phase hepatic fibrogenesis caused by carbon tetrachloride. , 2002, Biochemical and biophysical research communications.

[24]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.

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

[26]  T Hashimoto,et al.  Defect in Peroxisome Proliferator-activated Receptor α-inducible Fatty Acid Oxidation Determines the Severity of Hepatic Steatosis in Response to Fasting* , 2000, The Journal of Biological Chemistry.

[27]  R. Caporale,et al.  Ligands of peroxisome proliferator-activated receptor gamma modulate profibrogenic and proinflammatory actions in hepatic stellate cells. , 2000, Gastroenterology.

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

[29]  P. Galtier,et al.  Peroxisome Proliferator-activated Receptor α-Isoform Deficiency Leads to Progressive Dyslipidemia with Sexually Dimorphic Obesity and Steatosis* , 1998, The Journal of Biological Chemistry.

[30]  J. Auwerx,et al.  The Organization, Promoter Analysis, and Expression of the Human PPARγ Gene* , 1997, The Journal of Biological Chemistry.

[31]  J. Auwerx,et al.  Fibrates downregulate apolipoprotein C-III expression independent of induction of peroxisomal acyl coenzyme A oxidase. A potential mechanism for the hypolipidemic action of fibrates. , 1995, The Journal of clinical investigation.

[32]  Joel Z Stengel,et al.  Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. , 2011, Gastroenterology.