Targeting mitochondria to oppose the progression of nonalcoholic fatty liver disease.

Ignazio Grattagliano, Liliana P Montezinho, Paulo J Oliveira, Gema Frühbeck, Javier Gómez-Ambrosi, Fabrizio Montecucco, Federico Carbone, Mariusz R Wieckowski, David Q-H Wang, Piero Portincasa

Journal: Biochemical pharmacology 2019;160():34-45

PMID: 30508523

Full Text on Elsevier Science View on PubMed

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a condition characterized by the excessive accumulation of triglycerides in hepatocytes. NAFLD is the most frequent chronic liver disease in developed countries, and is often associated with metabolic disorders such as obesity and type 2 diabetes. NAFLD definition encompasses a spectrum of chronic liver abnormalities, ranging from simple steatosis (NAFL), to steatohepatitis (NASH), significant liver fibrosis, cirrhosis, and hepatocellular carcinoma. NAFLD, therefore, represents a global public health issue. Mitochondrial dysfunction occurs in NAFLD, and contributes to the progression to the necro-inflammatory and fibrotic form (NASH). Disrupted mitochondrial function is associated with a decrease in the energy levels and impaired redox balance, and negatively affects cell survival by altering overall metabolism and subcellular trafficking. Such events reduce the tolerance of hepatocytes towards damaging hits, and favour the injurious effects of extra-cellular factors. Here, we discuss the role of mitochondria in NAFLD and focus on potential therapeutic approaches aimed at preserving mitochondrial function.

Address: Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Bari, Italy; Italian College of General Practitioners and Primary Care, Bari, Italy.; CNC Center for Neuroscience and Cell Biology, University of Coimbra, UC-Biotech Building, Biocant Park, Cantanhede, Portugal; Center for Investigation Vasco da Gama (CIVG), Department of Veterinary Medicine, Escola Universitária Vasco da Gama, Coimbra, Portugal.; CNC Center for Neuroscience and Cell Biology, University of Coimbra, UC-Biotech Building, Biocant Park, Cantanhede, Portugal.; Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Pamplona, Spain; Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain; Department of Endocrinology & Nutrition, Clínica Universidad de Navarra, Pamplona, Spain.; Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Pamplona, Spain; Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.; First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy; Ospedale Policlinico San Martino, 10 Largo Benzi, 16132 Genoa, Italy; Centre of Excellence for Biomedical Research (CEBR), University of Genoa, 9 Viale Benedetto XV, 16132 Genoa, Italy.; First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy.; Nencki Institute of Experimental Biology, PAS, Warsaw, Poland.; Department of Medicine, Division of Gastroenterology and Liver Diseases, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, USA.; Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, University of Bari Medical School, Bari, Italy. Electronic address: [email protected].

DOI: 10.1016/j.bcp.2018.11.020

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MeSH Terms: Hepatocytes, Humans, Mitochondria, Liver, Non-alcoholic Fatty Liver Disease, Oxidation-Reduction