scholarly journals Etiopathogenesis of Nonalcoholic Steatohepatitis: Role of Obesity, Insulin Resistance and Mechanisms of Hepatotoxicity

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Praveen Guturu ◽  
Andrea Duchini
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Nonalcoholic Steatohepatitis ◽  
Molecular Mechanisms ◽  
Hepatocellular Cancer ◽  
Special Focus ◽  
Nonalcoholic Fatty Liver ◽  
New Treatments ◽  
Developed Nations

Incidence of nonalcoholic fatty liver disease is increasing with an estimated prevalence of 20–30% in developed nations. This is leading to increased incidence of chronic liver disease, cirrhosis, and hepatocellular cancer. It is critical to understand the etiology and pathogenesis of any disease to create therapeutic targets and develop new treatments. In this paper we discuss the etiology and pathogenesis of nonalcoholic steatohepatitis with special focus on obesity, role of insulin resistance, and molecular mechanisms of hepatotoxicity.

scholarly journals Targeting of Secretory Proteins as a Therapeutic Strategy for Treatment of Nonalcoholic Steatohepatitis (NASH)

2020 ◽  
Vol 21 (7) ◽  
pp. 2296
Author(s):  
Kyeongjin Kim ◽  
Kook Hwan Kim
Keyword(s):  
Liver Disease ◽  
Nonalcoholic Steatohepatitis ◽  
Therapeutic Strategy ◽  
Molecular Mechanisms ◽  
Liver Steatosis ◽  
Secretory Protein ◽  
Secretory Proteins ◽  
Therapeutic Approaches ◽  
Nonalcoholic Fatty Liver

Nonalcoholic steatohepatitis (NASH) is defined as a progressive form of nonalcoholic fatty liver disease (NAFLD) and is a common chronic liver disease that causes significant worldwide morbidity and mortality, and has no approved pharmacotherapy. Nevertheless, growing understanding of the molecular mechanisms underlying the development and progression of NASH has suggested multiple potential therapeutic targets and strategies to treat this disease. Here, we review this progress, with emphasis on the functional role of secretory proteins in the development and progression of NASH, in addition to the change of expression of various secretory proteins in mouse NASH models and human NASH subjects. We also highlight secretory protein-based therapeutic approaches that influence obesity-associated insulin resistance, liver steatosis, inflammation, and fibrosis, as well as the gut–liver and adipose–liver axes in the treatment of NASH.

scholarly journals Role of insulin resistance in the pathogenesis of nonalcoholic fatty liver disease

2010 ◽  
Vol 18 (30) ◽  
pp. 3175
Author(s):  
Bing-Fang Wang ◽  
Pei-Ying Tian ◽  
Kun Feng ◽  
Fu-Rong Wu ◽  
Yong-Gao Lu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver

Role of nonalcoholic fatty liver disease in the development of insulin resistance and diabetes

2008 ◽  
Vol 2 (5) ◽  
pp. 705-711 ◽  
Author(s):  
Henning Grønbæk ◽  
Karen Louise Thomsen ◽  
Jørgen Rungby ◽  
Ole Schmitz ◽  
Hendrik Vilstrup
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver

scholarly journals Deficiency of the Purinergic Receptor 2X7 Attenuates Nonalcoholic Steatohepatitis Induced by High-Fat Diet: Possible Role of the NLRP3 Inflammasome

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Claudia Blasetti Fantauzzi ◽  
Stefano Menini ◽  
Carla Iacobini ◽  
Chiara Rossi ◽  
Eleonora Santini ◽  
...  
Keyword(s):  
Nonalcoholic Steatohepatitis ◽  
Nlrp3 Inflammasome ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Purinergic Receptor ◽  
High Fat ◽  
Liver Sinusoidal Endothelial Cells ◽  
Nonalcoholic Fatty Liver ◽  
Markers Of Inflammation

Molecular mechanisms driving transition from simple steatosis to nonalcoholic steatohepatitis (NASH), a critical step in the progression of nonalcoholic fatty liver disease (NAFLD) to cirrhosis, are poorly defined. This study aimed at investigating the role of the purinergic receptor 2X7 (PR2X7), through the NLRP3 inflammasome, in the development of NASH. To this end, mice knockout for the Pr2x7 gene (Pr2x7−/−) and coeval wild-type (WT) mice were fed a high-fat diet (HFD) or normal-fat diet for 16 weeks. NAFLD grade and stage were lower in Pr2x7−/− than WT mice, and only 1/7 Pr2x7−/− animals showed evidence of NASH, as compared with 4/7 WT mice. Molecular markers of inflammation, oxidative stress, and fibrosis were markedly increased in WT-HFD mice, whereas no or significantly reduced increments were detected in Pr2x7−/− animals, which showed also decreased modulation of genes of lipid metabolism. Deletion of Pr2x7 gene was associated with blunted or abolished activation of NLRP3 inflammasome and expression of its components, which were induced in liver sinusoidal endothelial cells challenged with appropriate stimuli. These data show that Pr2x7 gene deletion protects mice from HFD-induced NASH, possibly through blunted activation of NLRP3 inflammasome, suggesting that PR2X7 and NLRP3 may represent novel therapeutic targets.

scholarly journals Inflammation as a potential link between nonalcoholic fatty liver disease and insulin resistance

2013 ◽  
Vol 218 (3) ◽  
pp. R25-R36 ◽  
Author(s):  
Mohamed Asrih ◽  
François R Jornayvaz
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Metabolic Energy ◽  
Hepatic Insulin Resistance ◽  
Major Health Problem ◽  
Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD) has become a major health problem in developed countries. It has affected more than 30% of the general population and is commonly associated with insulin resistance, which is a major risk factor for the development of type 2 diabetes and a central feature of the metabolic syndrome. Furthermore, accumulating evidences reveal that NAFLD as well as insulin resistance is strongly related to inflammation. Cytokines and adipokines play a pivotal role in inflammatory processes. In addition, these inflammatory mediators regulate various functions including metabolic energy balance, inflammation, and immune response. However, their role in modulating ectopic lipids involved in the development of insulin resistance, such as diacylglycerols and ceramides, remains unknown. The aim of this review is first to describe the pathophysiology of insulin resistance in NAFLD. In particular, we discuss the role of ectopic lipid accumulation in the liver. Secondly, we also summarize recent findings emphasizing the role of main inflammatory markers in both NAFLD and insulin resistance and their potential role in modulating hepatic fat content in NAFLD and associated hepatic insulin resistance.

scholarly journals Fibrosis in genotype 3 chronic hepatitis C and nonalcoholic fatty liver disease: Role of insulin resistance and hepatic steatosis

Hepatology ◽  
2006 ◽  
Vol 44 (6) ◽  
pp. 1648-1655 ◽  
Author(s):  
Elisabetta Bugianesi ◽  
Gulio Marchesini ◽  
Elena Gentilcore ◽  
Ian Homer Y. Cua ◽  
Ester Vanni ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Chronic Hepatitis ◽  
Liver Disease ◽  
Hepatitis C ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Genotype 3 ◽  
Nonalcoholic Fatty Liver
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