scholarly journals The Role of Innate Immune Cells in Nonalcoholic Fatty Liver Disease

2021 ◽  
pp. 1-11
Author(s):  
Marina Nati ◽  
Kyoung-Jin Chung ◽  
Triantafyllos Chavakis

Nonalcoholic fatty liver disease (NAFLD) is a very common hepatic pathology featuring steatosis and is linked to obesity and related conditions, such as the metabolic syndrome. When hepatic steatosis is accompanied by inflammation, the disorder is defined as nonalcoholic steatohepatitis (NASH), which in turn can progress toward fibrosis development that can ultimately result in cirrhosis. Cells of innate immunity, such as neutrophils or macrophages, are central regulators of NASH-related inflammation. Recent studies utilizing new experimental technologies, such as single-cell RNA sequencing, have revealed substantial heterogeneity within the macrophage populations of the liver, suggesting distinct functions of liver-resident Kupffer cells and recruited monocyte-derived macrophages with regards to regulation of liver inflammation and progression of NASH pathogenesis. Herein, we discuss recent developments concerning the function of innate immune cell subsets in NAFLD and NASH.

2020 ◽  
Vol 16 ◽  
Author(s):  
Anna Bobrus- Chociej ◽  
Natalia Wasilewska ◽  
Marta Flisiak- Jackiewicz ◽  
Dariusz Lebensztejn

: Nonalcoholic fatty liver disease (NAFLD) is a main cause of chronic liver disease in children. With the global obesity epidemic, the prevalence of NAFLD is increasing both in industrialized and developing countries. NAFLD is a multisystem disorder and a hepatic manifestation of the metabolic syndrome. Growing scientific evidence suggests that NAFLD is an independent risk factor for cardiovascular disease. This paper briefly describes the current knowledge concerning the association between NAFLD and cardiac dysfunction in children.


Author(s):  
Søren Møller ◽  
Nina Kimer ◽  
Thit Kronborg ◽  
Josephine Grandt ◽  
Jens Dahlgaard Hove ◽  
...  

AbstractNonalcoholic fatty liver disease (NAFLD) denotes a condition with excess fat in the liver. The prevalence of NAFLD is increasing, averaging > 25% of the Western population. In 25% of the patients, NAFLD progresses to its more severe form: nonalcoholic steatohepatitis and >25% of these progress to cirrhosis following activation of inflammatory and fibrotic processes. NAFLD is associated with obesity, type 2 diabetes, and the metabolic syndrome and represents a considerable and increasing health burden. In the near future, NAFLD cirrhosis is expected to be the most common cause for liver transplantation. NAFLD patients have an increased risk of developing cardiovascular disease as well as liver-related morbidity. In addition, hepatic steatosis itself appears to represent an independent cardiovascular risk factor. In the present review, we provide an overview of the overlapping mechanisms and prevalence of NAFLD and cardiovascular disease.


2003 ◽  
Vol 98 (9) ◽  
pp. 2064-2071 ◽  
Author(s):  
Arun J. Sanyal ◽  
Melissa J. Contos ◽  
Richard K. Sterling ◽  
Velimir A. Luketic ◽  
Mitchell L. Shiffman ◽  
...  

2019 ◽  
Vol 39 (03) ◽  
pp. 291-300 ◽  
Author(s):  
Hannelie Korf ◽  
Markus Boesch ◽  
Lore Meelberghs ◽  
Schalk van der Merwe

AbstractNonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries that could lead to serious health problems including liver failure, cancer, or death. The term NAFLD includes a spectrum of disease states with histological features ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). A key aspect within this research field is the identification of pathogenic factors that trigger inflammation, thus fueling the transition from nonalcoholic fatty liver to NASH. These inflammatory triggers may originate from within the liver as a result of innate immune cell activation and/or hepatocyte injury. Additionally, they may originate from other sites such as adipose tissue or the intestinal tract. In the current review, the authors will primarily focus on events within adipose tissue which may be of importance in triggering the disease progression. They specifically focus on the role of adipose tissue macrophages during NAFLD pathogenesis and how microenvironmental factors may shape their metabolic profile. They further dissect how redirecting the macrophage's metabolic profile alters their immunological functions. Finally, they discuss the opportunities and challenges of targeting macrophages to interfere in disease progression.


2019 ◽  
Vol 316 (4) ◽  
pp. G462-G472 ◽  
Author(s):  
Malte P. Suppli ◽  
Kristoffer T. G. Rigbolt ◽  
Sanne S. Veidal ◽  
Sara Heebøll ◽  
Peter Lykke Eriksen ◽  
...  

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of conditions ranging from simple steatosis (NAFL), over nonalcoholic steatohepatitis (NASH) with or without fibrosis, to cirrhosis with end-stage disease. The hepatic molecular events underlying the development of NAFLD and transition to NASH are poorly understood. The present study aimed to determine hepatic transcriptome dynamics in patients with NAFL or NASH compared with healthy normal-weight and obese individuals. RNA sequencing and quantitative histomorphometry of liver fat, inflammation and fibrosis were performed on liver biopsies obtained from healthy normal-weight ( n = 14) and obese ( n = 12) individuals, NAFL ( n = 15) and NASH ( n = 16) patients. Normal-weight and obese subjects showed normal liver histology and comparable gene expression profiles. Liver transcriptome signatures were largely overlapping in NAFL and NASH patients, however, clearly separated from healthy normal-weight and obese controls. Most marked pathway perturbations identified in both NAFL and NASH were associated with markers of lipid metabolism, immunomodulation, extracellular matrix remodeling, and cell cycle control. Interestingly, NASH patients with positive Sonic hedgehog hepatocyte staining showed distinct transcriptome and histomorphometric changes compared with NAFL. In conclusion, application of immunohistochemical markers of hepatocyte injury may serve as a more objective tool for distinguishing NASH from NAFL, facilitating improved resolution of hepatic molecular changes associated with progression of NAFLD. NEW & NOTEWORTHY Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries. NAFLD is associated with the metabolic syndrome and can progress to the more serious form, nonalcoholic steatohepatitis (NASH), and ultimately lead to irreversible liver damage. Using gold standard molecular and histological techniques, this study demonstrates that the currently used diagnostic tools are problematic for differentiating mild NAFLD from NASH and emphasizes the marked need for developing improved histological markers of NAFLD progression.


2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Nancy Magee ◽  
An Zou ◽  
Yuxia Zhang

Nonalcoholic fatty liver disease (NAFLD) is the most common type of chronic liver disease in the Western countries, affecting up to 25% of the general population and becoming a major health concern in both adults and children. NAFLD encompasses the entire spectrum of fatty liver disease in individuals without significant alcohol consumption, ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) and cirrhosis. NASH is a manifestation of the metabolic syndrome and hepatic disorders with the presence of steatosis, hepatocyte injury (ballooning), inflammation, and, in some patients, progressive fibrosis leading to cirrhosis. The pathogenesis of NASH is a complex process and implicates cell interactions between liver parenchymal and nonparenchymal cells as well as crosstalk between various immune cell populations in liver. Lipotoxicity appears to be the central driver of hepatic cellular injury via oxidative stress and endoplasmic reticulum (ER) stress. This review focuses on the contributions of hepatocytes and nonparenchymal cells to NASH, assessing their potential applications to the development of novel therapeutic agents. Currently, there are limited pharmacological treatments for NASH; therefore, an increased understanding of NASH pathogenesis is pertinent to improve disease interventions in the future.


2005 ◽  
Vol 90 (3) ◽  
pp. 1578-1582 ◽  
Author(s):  
F. Angelico ◽  
M. Del Ben ◽  
R. Conti ◽  
S. Francioso ◽  
K. Feole ◽  
...  

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.


2009 ◽  
Vol 35 (03) ◽  
pp. 277-287 ◽  
Author(s):  
Giovanni Targher ◽  
Michel Chonchol ◽  
Luca Miele ◽  
Giacomo Zoppini ◽  
Isabella Pichiri ◽  
...  

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