The Neglected Role of Bile Duct Epithelial Cells in NASH

2021 ◽  
Author(s):  
Massimiliano Cadamuro ◽  
Alberto Lasagni ◽  
Samantha Sarcognato ◽  
Maria Guido ◽  
Roberto Fabris ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Biological Effects ◽  
Cell Compartment ◽  
Ductular Reaction ◽  
Severe Condition ◽  
Nonalcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
The Common

AbstractNonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, and affects 25% of the population in Western countries. NAFLD is the hepatic manifestation of the metabolic syndrome, linked to insulin resistance, which is the common pathogenetic mechanism. In approximately 40% of NAFLD patients, steatosis is associated with necro-inflammation and fibrosis, resulting in nonalcoholic steatohepatitis (NASH), a severe condition that may progress to cirrhosis and liver cancer. Although the hepatocyte represents the main target of the disease, involvement of the bile ducts occurs in a subset of patients with NASH, and is characterized by ductular reaction and activation of the progenitor cell compartment, which incites portal fibrosis and disease progression. We aim to dissect the multiple biological effects that adipokines and metabolic alterations exert on cholangiocytes to derive novel information on the mechanisms driven by insulin resistance, which promote fibro-inflammation and carcinogenesis in 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

scholarly journals Adipokines in Nonalcoholic Steatohepatitis: From Pathogenesis to Implications in Diagnosis and Therapy

2009 ◽  
Vol 2009 ◽  
pp. 1-8 ◽  
Author(s):  
Emmanuel A. Tsochatzis ◽  
George V. Papatheodoridis ◽  
Athanasios J. Archimandritis
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Experimental Models ◽  
Liver Fat ◽  
Nonalcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
Noninvasive Markers ◽  
End Stage ◽  
Multiple Hit

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and can vary from benign steatosis to end-stage liver disease. The pathogenesis of non-alcoholic steatohepatitis (NASH) is currently thought to involve a multiple-hit process with the first hit being the accumulation of liver fat which is followed by the development of necroinflammation and fibrosis. There is mounting evidence that cytokines secreted from adipose tissue, namely, adipokines, are implicated in the pathogenesis and progression of NAFLD. In the current review, we explore the role of these adipokines, particularly leptin, adiponectin, resistin, tumor necrosis factor-a, and interleukin-6 in NASH, as elucidated in experimental models and clinical practice. We also comment on their potential use as noninvasive markers for differentiating simple fatty liver from NASH as well as on their potential future therapeutic role in patients with NASH.

scholarly journals Insulin Resistance, the Metabolic Syndrome, and Nonalcoholic Fatty Liver Disease

2005 ◽  
Vol 90 (3) ◽  
pp. 1578-1582 ◽  
Author(s):  
F. Angelico ◽  
M. Del Ben ◽  
R. Conti ◽  
S. Francioso ◽  
K. Feole ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Oral Glucose ◽  
Nonalcoholic Fatty Liver ◽  
Insulin Resistant ◽  
The Metabolic Syndrome

Background/Aims: An association of nonalcoholic fatty liver disease with the insulin-resistant metabolic syndrome has been suggested. The aim of the study was to assess the association of fatty liver to different degrees of insulin resistance and secretion. Methods and Results: The study was performed in 308 alcohol- and virus-negative consecutive patients attending a metabolic clinic, who underwent a complete clinical and biochemical work-up including oral glucose tolerance test and routine liver ultrasonography. Steatosis was graded as absent/mild, moderate, and severe. In nondiabetic subjects, a progressive (P < 0.05) increase in mean homeostasis model of insulin resistance was recorded from the group without steatosis to the groups with mild/moderate and severe steatosis. Severe steatosis was associated with the clustering of the five clinical and biochemical features proposed for the clinical diagnosis of the metabolic syndrome. Subjects with the metabolic syndrome with a more pronounced insulin resistance had a higher prevalence of severe steatosis (P < 0.01) compared with those with homeostasis model of insulin resistance below the median. Conclusions: The findings stress the heterogeneous presentation of patients with the metabolic syndrome when the diagnosis is based on the broad Adult Treatment Panel III clinical criteria and demonstrate that those who are more insulin resistant have a higher prevalence of severe steatosis.

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 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

Role of physical activity in the treatment of nonalcoholic fatty liver disease in children and adolescents

2013 ◽  
Vol 38 (8) ◽  
pp. 805-812 ◽  
Author(s):  
Anthony R. Deldin ◽  
SoJung Lee
Keyword(s):  
Physical Activity ◽  
Insulin Resistance ◽  
Liver Disease ◽  
Children And Adolescents ◽  
Calorie Restriction ◽  
Fatty Liver Disease ◽  
Liver Fat ◽  
Obese Children ◽  
Nonalcoholic Fatty Liver

Currently, nonalcoholic fatty liver disease (NAFLD) is the most frequent liver abnormality observed in obese children and adolescents. A strong body of evidence suggests that increased liver fat is significantly associated with visceral adiposity, metabolic syndrome, and insulin resistance in obese children and adolescents. Diet and exercise are generally recommended to treat obese youth with NAFLD as they do not carry side effects and confer multiple cardiometabolic benefits. Studies in adult populations report a beneficial effect of regular physical activity on reducing liver fat. In children and adolescents, available data show that weight loss induced by increasing physical activity and calorie restriction is beneficial to reduce liver fat and associated health risk factors such as insulin resistance and dyslipidemia. Currently, evidence regarding the independent effects of regular exercise alone (e.g., without calorie restriction) on NAFLD are unclear. Additionally, there is no data regarding the optimal exercise regimen (e.g., type, dose, intensity) that should be prescribed for reducing NAFLD in children and adolescents. The purpose of this review is to examine the role of physical activity on NAFLD in children and adolescents.

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