title: Mitochondrial Adaptation in Nonalcoholic Fatty Liver Disease: Novel Mechanisms and Treatment Strategies.
abstract: Nonalcoholic fatty liver disease (NAFLD) is prevalent in patients with obesity or type 2 diabetes. Nonalcoholic steatohepatitis (NASH), encompassing steatosis with inflammation, hepatocyte injury, and fibrosis, predisposes to cirrhosis, hepatocellular carcinoma, and even cardiovascular disease. In rodent models and humans with NAFLD/NASH, maladaptation of mitochondrial oxidative flux is a central feature of simple steatosis to NASH transition. Induction of hepatic tricarboxylic acid cycle closely mirrors the severity of oxidative stress and inflammation in NASH. Reactive oxygen species generation and inflammation are driven by upregulated, but inefficient oxidative flux and accumulating lipotoxic intermediates. Successful therapies for NASH (weight loss alone or with incretin therapy, or pioglitazone) likely attenuate mitochondrial oxidative flux and halt hepatocellular injury. Agents targeting mitochondrial dysfunction may provide a novel treatment strategy for NAFLD.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, University of Florida, 1600 SW Archer Road, Room H-2, Gainesville, FL 32610, USA.
authors.forename: Nishanth E
authors.initials: NE
authors.lastname: Sunny
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, University of Florida, 1600 SW Archer Road, Room H-2, Gainesville, FL 32610, USA.
authors.forename: Fernando
authors.initials: F
authors.lastname: Bril
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, University of Florida, 1600 SW Archer Road, Room H-2, Gainesville, FL 32610, USA; Malcom Randall Veterans Administration Medical Center, Gainesville, FL, USA. Electronic address: Kenneth.Cusi@medicine.ufl.edu.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Cusi
mesh_terms: D000818:Animals; D005234:Fatty Liver / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology*; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use
chemical_list: D045162:Thiazolidinediones; D052216:Glucagon-Like Peptide 1; D000077205:Pioglitazone
keywords: diabetes; fatty liver; glucagon-like peptide-1; mitochondria; nonalcoholic steatohepatitis; obesity; pioglitazone