Remodeling of Mitochondrial Plasticity: The Key Switch from NAFLD/NASH to HCC.
TLDR
This review will discuss how mitochondrial defects may be translated into causative explanations of NAFLD-driven HCC, emphasizing future directions for research purposes and for development of potential preventive or curative strategies.Abstract:
Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and the third-leading cause of cancer-related mortality Currently, the global burden of nonalcoholic fatty liver disease (NAFLD) has dramatically overcome both viral and alcohol hepatitis, thus becoming the main cause of HCC incidence NAFLD pathogenesis is severely influenced by lifestyle and genetic predisposition Mitochondria are highly dynamic organelles that may adapt in response to environment, genetics and epigenetics in the liver (“mitochondrial plasticity”) Mounting evidence highlights that mitochondrial dysfunction due to loss of mitochondrial flexibility may arise before overt NAFLD, and from the early stages of liver injury Mitochondrial failure promotes not only hepatocellular damage, but also release signals (mito-DAMPs), which trigger inflammation and fibrosis, generating an adverse microenvironment in which several hepatocytes select anti-apoptotic programs and mutations that may allow survival and proliferation Furthermore, one of the key events in malignant hepatocytes is represented by the remodeling of glucidic–lipidic metabolism combined with the reprogramming of mitochondrial functions, optimized to deal with energy demand In sum, this review will discuss how mitochondrial defects may be translated into causative explanations of NAFLD-driven HCC, emphasizing future directions for research and for the development of potential preventive or curative strategiesread more
Citations
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Oxidative Stress in Non-Alcoholic Fatty Liver Disease
Carlo Smirne,Eleonora Croce,D. Di Benedetto,Vincenzo Cantaluppi,Cristoforo Comi,Pier Paolo Sainaghi,Rosalba Minisini,Elena Grossini,Mario Pirisi +8 more
TL;DR: This review highlights the interaction between oxidative stress (OS) and disturbed lipid metabolism and proposes new therapeutic approaches targeting the gut microbiota dysbiosis, including probiotics, prebiotics, diet, and fecal microbiota transplantation.
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The Saga of Endocrine FGFs.
Phuc Phan,Bibhuti Ballav Saikia,Shivakumar Sonnaila,Shilpi Agrawal,Zeina Alraawi,Thallapuranam Krishnaswamy Suresh Kumar,Shilpa Iyer +6 more
TL;DR: A comprehensive review of the history, structure-function relationship(s), downstream signaling, physiological roles, and future perspectives on endocrine FGFs is provided in this paper, where two members of the klotho family act as main cofactors which can scaffold to tether FGF19/21/23 to their receptor(s) to form an active complex.
Journal ArticleDOI
Non-Alcoholic Steatohepatitis (NASH) and Organokines: What Is Now and What Will Be in the Future
João Paulo Margiotti Dos Santos,Mariana Canevari de Maio,Monike Alves Lemes,Lucas Fornari Laurindo,Jesselina Francisco dos Santos Haber,Marcelo Dib Bechara,Pedro Sidnei do Prado,Eduardo Costa Rauen,Fernando Teixeira Costa,Barbara Cristina de Abreu Pereira,Uri Adrian Prync Flato,Ricardo de Alvares Goulart,Eduardo Federighi Baisi Chagas,Sandra Maria Barbalho +13 more
TL;DR: Further studies involving skeletal muscle, adipose, bone, and liver tissue as endocrine organs are essential to better understand the modulation of organokines involved in the pathogenesis of NASH to advance in the treatment of this disease.
Journal ArticleDOI
Mitochondrial Mechanisms of Apoptosis and Necroptosis in Liver Diseases
TL;DR: In this article, the role of mitochondria in cell death and the mechanism that leads to chronic liver hepatitis and liver cirrhosis was discussed, and therapeutic strategies for targeting mitochondrial-mediated cell death in liver diseases were discussed.
Journal ArticleDOI
Epidemiologic, Genetic, Pathogenic, Metabolic, Epigenetic Aspects Involved in NASH-HCC: Current Therapeutic Strategies
Jorge Gutiérrez-Cuevas,Silvia Lucano-Landeros,D. López-Cifuentes,Arturo Santos,Juan Armendáriz-Borunda +4 more
TL;DR: In this article , the authors discuss the current molecular data supporting the link between HCC and NASH, with a focus on metabolic alterations, genetic and epigenetic drivers, including current therapeutic strategies for NASH and HCC prevention and treatment.
References
More filters
Journal ArticleDOI
EASL-EORTC clinical practice guidelines : management of hepatocellular carcinoma
Peter R. Galle,Alejandro Forner,Josep M. Llovet,Vincenzo Mazzaferro,Fabio Piscaglia,Jean-Luc Raoul,Peter Schirmacher,Valérie Vilgrain +7 more
TL;DR: The following Clinical Practice Guidelines will give up-to-date advice for the clinical management of patients with hepatocellular carcinoma, as well as providing an in-depth review of all the relevant data leading to the conclusions herein.
Journal ArticleDOI
Global epidemiology of nonalcoholic fatty liver disease—Meta‐analytic assessment of prevalence, incidence, and outcomes
Zobair M. Younossi,Zobair M. Younossi,Aaron B. Koenig,Dinan Abdelatif,Yousef Fazel,Linda Henry,Mark Wymer,Mark Wymer +7 more
TL;DR: As the global epidemic of obesity fuels metabolic conditions, the clinical and economic burden of NAFLD will become enormous, and random‐effects models were used to provide point estimates of prevalence, incidence, mortality and incidence rate ratios.
Journal ArticleDOI
Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement.
Scott M. Grundy,James I. Cleeman,Stephen R. Daniels,Karen A. Donato,Robert H. Eckel,Barry A. Franklin,David Gordon,Ronald M. Krauss,Peter J. Savage,Sidney C. Smith,John A. Spertus,Fernando Costa +11 more
TL;DR: This statement from the American Heart Association and the National Heart, Lung, and Blood Institute is intended to provide up-to-date guidance for professionals on the diagnosis and management of the metabolic syndrome in adults.
Journal ArticleDOI
Endoplasmic Reticulum Stress Links Obesity, Insulin Action, and Type 2 Diabetes
Umut Ozcan,Qiong Cao,Erkan Yilmaz,Ann-Hwee Lee,Neal N. Iwakoshi,Esra Özdelen,Gurol Tuncman,Cem Z. Görgün,Laurie H. Glimcher,Gökhan S. Hotamisligil +9 more
TL;DR: It is shown that obesity causes endoplasmic reticulum (ER) stress, which leads to suppression of insulin receptor signaling through hyperactivation of c-Jun N-terminal kinase (JNK) and subsequent serine phosphorylation of insulin receptors substrate–1 (IRS-1).
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