Journal ArticleDOI
Mitochondrial Adaptation in Nonalcoholic Fatty Liver Disease: Novel Mechanisms and Treatment Strategies
TLDR
Agents targeting mitochondrial dysfunction may provide a novel treatment strategy for NAFLD and halt hepatocellular injury.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.read more
Citations
More filters
Journal ArticleDOI
From NASH to HCC: current concepts and future challenges.
Quentin M. Anstee,Quentin M. Anstee,Helen L. Reeves,Helen L. Reeves,Elena Kotsiliti,Olivier Govaere,Mathias Heikenwalder +6 more
TL;DR: This Review discusses NAFLD-associated HCC, including its epidemiology, key features that promote hepatocarcinogenesis and the management of HCC in patients with obesity and associated metabolic comorbidities, and the challenges and future directions of research.
Journal ArticleDOI
Lipotoxicity and the gut-liver axis in NASH pathogenesis
TL;DR: The initial mechanisms responsible for hepatocellular damage and inflammation, which derive from the toxic effects of excess lipids, are analyzed and accumulating data indicate that the total amount of triglycerides stored in hepatocytes is not the major determinant of lipotoxicity.
Journal ArticleDOI
Role of oxidative stress in the pathogenesis of nonalcoholic fatty liver disease.
TL;DR: This review summarizes the mechanisms that may account for the excessive production of ROS, the potential mechanistic roles of ROS that drive NAFLD progression, and therapeutic interventions that are related to oxidative stress.
Journal ArticleDOI
Effects of dapagliflozin and n-3 carboxylic acids on non-alcoholic fatty liver disease in people with type 2 diabetes: a double-blind randomised placebo-controlled study.
Jan W. Eriksson,Per Lundkvist,Per-Anders Jansson,Lars Johansson,Mats Kvarnström,Linda Moris,Tasso Miliotis,Gun-Britt Forsberg,Ulf Risérus,Lars Lind,Jan Oscarsson +10 more
TL;DR: Combined treatment with dapagliflozin and OM-3CA significantly reduced liver fat content and monotherapy reduced all measured hepatocyte injury biomarkers and FGF21, suggesting a disease-modifying effect in NAFLD.
Journal ArticleDOI
Nonalcoholic Fatty Liver Disease: Basic Pathogenetic Mechanisms in the Progression From NAFLD to NASH
TL;DR: In this paper, the pathogenesis of NAFLD and the mechanisms behind its progression to NASH have been extensively studied, although the processes that determine fat accumulation are mostly clear, the mechanisms associated with the progression of the disease are not fully characterized.
References
More filters
Journal ArticleDOI
Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes
Steven P. Marso,Gilbert H. Daniels,Kirstine Brown-Frandsen,Peter Lommer Kristensen,Johannes F.E. Mann,Michael A. Nauck,Steven E. Nissen,Stuart J. Pocock,Neil R Poulter,Lasse Steen Ravn,William M. Steinberg,Mette Stockner,Bernard Zinman,Richard M. Bergenstal,John B. Buse +14 more
TL;DR: In the time-to-event analysis, the rate of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, orNonfatal stroke among patients with type 2 diabetes mellitus was lower with liraglutide than with placebo.
Journal ArticleDOI
The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association
Naga Chalasani,Zobair M. Younossi,Joel E. Lavine,Anna Mae Diehl,Elizabeth M. Brunt,Kenneth Cusi,Michael Charlton,Arun J. Sanyal +7 more
TL;DR: This is a practice guideline for clinicians rather than a review article and interested readers can refer to several comprehensive reviews published recently.
Journal ArticleDOI
EASL-EASD-EASO Clinical Practice Guidelines for the Management of Non-Alcoholic Fatty Liver Disease
Giulio Marchesini,Christopher P. Day,Jean-François Dufour,Ali Canbay,Valerio Nobili,Vlad Ratziu,Herbert Tilg,Michael Roden,Amalia Gastaldelli,Hannele Yki-Järvinen,Fritz Schick,Roberto Vettor,Gema Frühbeck,Lisbeth Mathus-Vliegen +13 more
TL;DR: The final purpose is to improve patient care and awareness of the importance of NAFLD, and to assist stakeholders in the decision-making process by providing evidence-based data, which also takes into consideration the burden of clinical management for the healthcare system.
Journal ArticleDOI
Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease.
Kerry L. Donnelly,Coleman Smith,Sarah Jane Schwarzenberg,Jose Jessurun,Mark D. Boldt,Elizabeth J. Parks +5 more
TL;DR: In this article, the authors quantified the biological sources of hepatic and plasma lipoprotein TAG in NAFLD patients, using stable isotopes for four days to label and track serum nonesterified fatty acids (NEFAs), dietary fatty acids, and those derived from the de novo lipogenesis (DNL) pathway, present in liver tissue and lipid TAG.
Journal ArticleDOI
Pioglitazone, Vitamin E, or Placebo for Nonalcoholic Steatohepatitis
Arun J. Sanyal,Naga Chalasani,Kris V. Kowdley,Arthur J. McCullough,Anna Mae Diehl,Nathan M. Bass,Brent A. Neuschwander-Tetri,Joel E. Lavine,James Tonascia,Aynur Unalp,Mark L. Van Natta,Jeanne M. Clark,Elizabeth M. Brunt,David E. Kleiner,Jay H. Hoofnagle,Patricia R. Robuck +15 more
TL;DR: Vitamin E was superior to placebo for the treatment of nonalcoholic steatohepatitis in adults without diabetes, and significant benefits of pioglitazone were observed for some of the secondary outcomes.