학술논문
Metabolic Injury of Hepatocytes Promotes Progression of NAFLD and AALD.
Document Type
Academic Journal
Author
Carvalho-Gontijo R; Department of Medicine, University of California, San Diego School of Medicine, La Jolla, California.; Department of Surgery, University of California, San Diego School of Medicine, La Jolla, California.; Han C; Department of Medicine, University of California, San Diego School of Medicine, La Jolla, California.; Department of Surgery, University of California, San Diego School of Medicine, La Jolla, California.; Zhang L; Department of Medicine, University of California, San Diego School of Medicine, La Jolla, California.; Department of Surgery, University of California, San Diego School of Medicine, La Jolla, California.; Zhang V; Department of Medicine, University of California, San Diego School of Medicine, La Jolla, California.; Department of Surgery, University of California, San Diego School of Medicine, La Jolla, California.; Hosseini M; Department of Pathology, University of California, San Diego School of Medicine, La Jolla, California.; Mekeel K; Department of Surgery, University of California, San Diego School of Medicine, La Jolla, California.; Schnabl B; Department of Medicine, University of California, San Diego School of Medicine, La Jolla, California.; Loomba R; Department of Medicine, University of California, San Diego School of Medicine, La Jolla, California.; Karin M; Department of Pharmacology, University of California, San Diego School of Medicine, La Jolla, California.; Brenner DA; Department of Medicine, University of California, San Diego School of Medicine, La Jolla, California.; Kisseleva T; Department of Surgery, University of California, San Diego School of Medicine, La Jolla, California.
Source
Publisher: Thieme Country of Publication: United States NLM ID: 8110297 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1098-8971 (Electronic) Linking ISSN: 02728087 NLM ISO Abbreviation: Semin Liver Dis Subsets: MEDLINE
Subject
Language
English
Abstract
Nonalcoholic liver disease is a component of metabolic syndrome associated with obesity, insulin resistance, and hyperlipidemia. Excessive alcohol consumption may accelerate the progression of steatosis, steatohepatitis, and fibrosis. While simple steatosis is considered a benign condition, nonalcoholic steatohepatitis with inflammation and fibrosis may progress to cirrhosis, liver failure, and hepatocellular cancer. Studies in rodent experimental models and primary cell cultures have demonstrated several common cellular and molecular mechanisms in the pathogenesis and regression of liver fibrosis. Chronic injury and death of hepatocytes cause the recruitment of myeloid cells, secretion of inflammatory and fibrogenic cytokines, and activation of myofibroblasts, resulting in liver fibrosis. In this review, we discuss the role of metabolically injured hepatocytes in the pathogenesis of nonalcoholic steatohepatitis and alcohol-associated liver disease. Specifically, the role of chemokine production and de novo lipogenesis in the development of steatotic hepatocytes and the pathways of steatosis regulation are discussed.
Competing Interests: R.L. serves as a consultant for Aardvark Therapeutics, Altimmune, Anylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Bristol-Myer Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse bio, Hightide, Inipharm, Intercept, Inventiva, Ionis, Janssen Inc., Madrigal, Metacrine, Inc., NGM Biopharmaceuticals, Novartis, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89 bio, and Viking Therapeutics. In addition, his institution has received grant support from Allergan, Astrazeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galectin Therapeutics, Galmed Pharmaceuticals, Genfit, Gilead, Intercept, Inventiva, Janssen, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, Pfizer, and Sonic Incytes. He is also cofounder of Liponexus, Inc. B.S. has been consulting for Ferring Research Institute, Gelesis, HOST Therabiomics, Intercept Pharmaceuticals, Mabwell Therapeutics, Patara Pharmaceuticals, and Takeda. B.S. is founder of Nterica Bio. UC San Diego has filed several patents with B.S. as inventor related to this work. B.S.'s institution UC San Diego has received research support from Axial Biotherapeutics, BiomX, CymaBay Therapeutics, NGM Biopharmaceuticals, Prodigy Biotech, and Synlogic Operating Company.
(Thieme. All rights reserved.)
Competing Interests: R.L. serves as a consultant for Aardvark Therapeutics, Altimmune, Anylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Bristol-Myer Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse bio, Hightide, Inipharm, Intercept, Inventiva, Ionis, Janssen Inc., Madrigal, Metacrine, Inc., NGM Biopharmaceuticals, Novartis, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89 bio, and Viking Therapeutics. In addition, his institution has received grant support from Allergan, Astrazeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galectin Therapeutics, Galmed Pharmaceuticals, Genfit, Gilead, Intercept, Inventiva, Janssen, Madrigal Pharmaceuticals, Merck, NGM Biopharmaceuticals, Pfizer, and Sonic Incytes. He is also cofounder of Liponexus, Inc. B.S. has been consulting for Ferring Research Institute, Gelesis, HOST Therabiomics, Intercept Pharmaceuticals, Mabwell Therapeutics, Patara Pharmaceuticals, and Takeda. B.S. is founder of Nterica Bio. UC San Diego has filed several patents with B.S. as inventor related to this work. B.S.'s institution UC San Diego has received research support from Axial Biotherapeutics, BiomX, CymaBay Therapeutics, NGM Biopharmaceuticals, Prodigy Biotech, and Synlogic Operating Company.
(Thieme. All rights reserved.)