Abstract
Fatty liver disease is one of most prevalent metabolic liver diseases, which includes alcoholic (ASH) and nonalcoholic steatohepatitis (NASH). Its initial stage is characterized by fat accumulation in the liver, that can progress to steatohepatitis, a stage of the disease in which steatosis is accompanied by inflammation, hepatocellular death, oxidative stress and fibrosis. Recent evidence in experimental models as well as in patients with steatohepatitis have uncovered a role for cholesterol and sphingolipids, particularly ceramide, in the transition from steatosis to steatohepatitis, insulin resistance and hence disease progression. Cholesterol accumulation and its trafficking to mitochondria sensitizes fatty liver to subsequent hits including inflammatory cytokines, such as TNF/Fas, in a pathway involving ceramide generation by acidic sphingomyelinase (ASMase). Thus, targeting both cholesterol and/or ASMase may represent a novel therapeutic approach of relevance in ASH and NASH, two of the most common forms of liver diseases worldwide.
Keywords: mitochondria, cholesterol, oxidative stress, steatohepatitis, cell death, sphingolipids, Nitric oxide, peroxynitrite, free radicals, antioxidants, nitrotyrosine, oxidation, nitration, fibrinogen
Current Pharmaceutical Design
Title: Metabolic Therapy: Lessons from Liver Diseases
Volume: 17 Issue: 35
Author(s): Carmen Garcia-Ruiz, Montserrat Mari, Anna Colell, Albert Morales and Jose C. Fernandez-Checa
Affiliation:
Keywords: mitochondria, cholesterol, oxidative stress, steatohepatitis, cell death, sphingolipids, Nitric oxide, peroxynitrite, free radicals, antioxidants, nitrotyrosine, oxidation, nitration, fibrinogen
Abstract: Fatty liver disease is one of most prevalent metabolic liver diseases, which includes alcoholic (ASH) and nonalcoholic steatohepatitis (NASH). Its initial stage is characterized by fat accumulation in the liver, that can progress to steatohepatitis, a stage of the disease in which steatosis is accompanied by inflammation, hepatocellular death, oxidative stress and fibrosis. Recent evidence in experimental models as well as in patients with steatohepatitis have uncovered a role for cholesterol and sphingolipids, particularly ceramide, in the transition from steatosis to steatohepatitis, insulin resistance and hence disease progression. Cholesterol accumulation and its trafficking to mitochondria sensitizes fatty liver to subsequent hits including inflammatory cytokines, such as TNF/Fas, in a pathway involving ceramide generation by acidic sphingomyelinase (ASMase). Thus, targeting both cholesterol and/or ASMase may represent a novel therapeutic approach of relevance in ASH and NASH, two of the most common forms of liver diseases worldwide.
Export Options
About this article
Cite this article as:
Garcia-Ruiz Carmen, Mari Montserrat, Colell Anna, Morales Albert and C. Fernandez-Checa Jose, Metabolic Therapy: Lessons from Liver Diseases, Current Pharmaceutical Design 2011; 17 (35) . https://dx.doi.org/10.2174/138161211798357700
DOI https://dx.doi.org/10.2174/138161211798357700 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Halogenated Agents and Cardiovascular Surgery: Has Mortality Really Decreased?
Current Vascular Pharmacology Cutaneous Complications of Anderson-Fabry Disease
Current Pharmaceutical Design Nuclear Medicine: Proof of Principle for Targeted Drugs in Diagnosis and Therapy
Current Pharmaceutical Design Unusual Clinical Manifestations of the Antiphospholipid Syndrome
Current Rheumatology Reviews Natural AMPK Activators: An Alternative Approach for the Treatment and Management of Metabolic Syndrome
Current Medicinal Chemistry Neuroprotective Effects of Ginkgolide B Against Ischemic Stroke: A Review of Current Literature
Current Topics in Medicinal Chemistry Mediterranean Diet and Dementia of the Alzheimer Type
Current Aging Science SAR, Cardiac Myocytes Protection Activity and 3D-QSAR Studies of Salubrinal and its Potent Derivatives
Current Medicinal Chemistry Imaging of Organ Metabolism in Obesity and Diabetes: Treatment Perspectives
Current Pharmaceutical Design Meet Our Editorial Board Member
Current Nanomedicine Diabetes Mellitus and Vascular Endothelial Dysfunction: Current Perspectives
Current Vascular Pharmacology Hypertension and Ischemic Heart Disease in Women
Current Pharmaceutical Design Hydrogen Sulphide: Biopharmacological Roles in the Cardiovascular System and Pharmaceutical Perspectives
Current Medicinal Chemistry AMPK As A Target in Rare Diseases
Current Drug Targets The Role of Anticoagulation in IPF
Current Respiratory Medicine Reviews Beta-Blockers in the Treatment of Dilated Cardiomyopathy: Which is the Best?
Current Pharmaceutical Design Processing of Amyloid Precursor Protein as a Biochemical Link Between Atherosclerosis and Alzheimers Disease
Cardiovascular & Hematological Disorders-Drug Targets Theory and Application of Microdialysis in Pharmacokinetic Studies
Current Drug Metabolism Chemotherapy and Cardiotoxicity in Hematologic Malignancies
Current Cancer Drug Targets Acute Coronary Syndrome and its Antithrombotic Treatment: Focus on Aspirin and Clopidogrel Resistance
Current Vascular Pharmacology