Hepatocyte Nicotinamide Adenine Dinucleotide Phosphate Reduced Oxidase 4 Regulates Stress Signaling, Fibrosis, and Insulin Sensitivity During Development of Steatohepatitis in Mice

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 149; no. 2; pp. 468 - 480.e10
• Main Authors: Bettaieb, Ahmed, Jiang, Joy X., Sasaki, Yu, Chao, Tzu-I, Kiss, Zsofia, Chen, Xiangling, Tian, Jijing, Katsuyama, Masato, Yabe-Nishimura, Chihiro, Xi, Yannan, Szyndralewiez, Cedric, Schröder, Kathrin, Shah, Ajay, Brandes, Ralph P., Haj, Fawaz G., Török, Natalie J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2015
• Subjects: Animals; Biomarkers - metabolism; Biopsy; Diet - methods; Disease Models, Animal; Fatty Liver - chemically induced; Fatty Liver - drug therapy; Fatty Liver - genetics; Fatty Liver - metabolism; Gastroenterology and Hepatology; Hepatocytes - drug effects; Hepatocytes - metabolism; Humans; Inflammation; Insulin Resistance; Lipid Peroxidation - drug effects; Liver - cytology; Liver - pathology; Liver Cirrhosis - drug therapy; Liver Cirrhosis - pathology; Mice; Mice, Inbred C57BL; Mice, Knockout; Mouse Model; NADP - administration & dosage; NADP - pharmacology; NADPH Oxidase 4; NADPH Oxidases - metabolism; Obesity; Obesity - drug therapy; Obesity - metabolism; Oxidative Stress - drug effects; Protein Phosphatase 1 - metabolism; Pyrazoles - metabolism; Pyrazolones; Pyridines - metabolism; Pyridones; Stress Signaling; Stress, Physiological - drug effects; Obesity; FFD; JNK; IR; Inflammation; IRS; PERK; NASH; ER; CSAA; TNF-α; PKR; NOX; ROS; CHOP; HSC; TGF-β; NOX4hepKO; Stress Signaling; CDAA; Mouse Model; nonalcoholic steatohepatitis; hepatocyte-specific deletion of nicotinamide adenine dinucleotide phosphate reduced oxidase 4; RNA-dependent protein kinase-like ER kinase; reactive oxidative species; hepatic stellate cell; NOX4 hepKO; insulin receptor substrate; c-jun-N-terminal kinase; nicotinamide adenine dinucleotide phosphate reduced oxidase; choline-deficient amino acid defined; CCAAT/enhancer-binding protein homologous protein; fast-food diet; choline-supplemented l-amino acid; transforming growth factor-β; tumor necrosis factor-α; insulin receptor; double-stranded RNA-activated protein kinase; endosplasmic reticulum

Reactive oxidative species (ROS) are believed to be involved in the progression of nonalcoholic steatohepatitis (NASH). However, little is known about the sources of ROS in hepatocytes or their role in disease progression. We studied the effects of nicotinamide adenine dinucleotide phosphate reduced...