scholarly journals Role of NKT Cells in the Pathogenesis of NAFLD

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Kazuto Tajiri ◽  
Yukihiro Shimizu
Keyword(s):  
Liver Disease ◽  
Early Stage ◽  
Critical Role ◽  
Inflammatory Cells ◽  
Nkt Cells ◽  
Protective Role ◽  
Nonalcoholic Fatty Liver ◽  
Progression Factor ◽  
Inflammatory Changes

Nonalcoholic fatty liver disease (NAFLD) is the most frequent chronic liver disease and shows various inflammatory changes in the liver. Among those inflammatory cells, natural killer T (NKT) cells are found to have a critical role during the disease progression. NKT cells may have a protective role at the early stage with simple steatosis through modification of insulin resistance, whereas they act as a progression factor at the advanced stage with fibrosis. Those processes are thought to depend on interaction between NKT cells and CD1d molecule in the liver.

scholarly journals Metabolic profiling reveals that PNPLA3 induces widespread effects on metabolism beyond triacylglycerol remodeling in Huh-7 hepatoma cells

2014 ◽  
Vol 307 (1) ◽  
pp. G66-G76 ◽  
Author(s):  
Hae-Ki Min ◽  
Silvia Sookoian ◽  
Carlos J. Pirola ◽  
Jianfeng Cheng ◽  
Faridoddin Mirshahi ◽  
...  
Keyword(s):  
Liver Disease ◽  
Metabolic Profiling ◽  
Critical Role ◽  
Fold Increase ◽  
Liver Metabolism ◽  
Hepatoma Cells ◽  
Triacylglycerol Lipase ◽  
Nonalcoholic Fatty Liver ◽  
Triglyceride Accumulation

PNPLA3 was recently associated with the susceptibility to nonalcoholic fatty liver disease, a common cause of chronic liver disease characterized by abnormal triglyceride accumulation. Although it is established that PNPLA3 has both triacylglycerol lipase and acylglycerol O-acyltransferase activities, is still unknown whether the gene has any additional role in the modulation of the human liver metabolome. To uncover the functional role of PNPLA3 on liver metabolism, we performed high-throughput metabolic profiling of PNPLA3 siRNA-silencing and overexpression of wild-type and mutant Ile148Met variants (isoleucine/methionine substitution at codon 148) in Huh-7 cells. Metabolomic analysis was performed by using GC/MS and LC/MS platforms. Silencing of PNPLA3 was associated with a global perturbation of Huh-7 hepatoma cells that resembled a catabolic response associated with protein breakdown. A significant decrease in amino- and γ-glutamyl-amino acids and dipeptides and a significant increase in cysteine sulfinic acid, myo-inositol, lysolipids, sphingolipids, and polyunsaturated fatty acids were observed. Overexpression of the PNPLA3 Met148 variant mirrored many of the metabolic changes observed during gene silencing, but in the opposite direction. These findings were replicated by the exploration of canonical pathways associated with PNPLA3 silencing and Met148 overexpression. Overexpression of the PNPLA3 Met148 variant was associated with a 1.75-fold increase in lactic acid, suggesting a shift to anaerobic metabolism and mitochondrial dysfunction. Together, these results suggest a critical role of PNPLA3 in the modulation of liver metabolism beyond its classical participation in triacylglycerol remodeling.

Protective Role of Dietary Capsanthin in a Mouse Model of Nonalcoholic Fatty Liver Disease

2021 ◽  
Vol 24 (6) ◽  
pp. 635-644
Author(s):  
Hee Kyoung Joo ◽  
Yu Ran Lee ◽  
Eun-Ok Lee ◽  
Sungmin Kim ◽  
Hao Jin ◽  
...  
Keyword(s):  
Liver Disease ◽  
Mouse Model ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Protective Role ◽  
Nonalcoholic Fatty Liver

scholarly journals The Potential Protective Role of RUNX1 in Nonalcoholic Fatty Liver Disease

2021 ◽  
Vol 22 (10) ◽  
pp. 5239
Author(s):  
Laia Bertran ◽  
Angela Pastor ◽  
Marta Portillo-Carrasquer ◽  
Jessica Binetti ◽  
Carmen Aguilar ◽  
...  
Keyword(s):  
Morbid Obesity ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Normal Liver ◽  
Protective Role ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Expression

The pathogenic mechanisms underlying nonalcoholic fatty liver disease (NAFLD) are beginning to be understood. RUNX1 is involved in angiogenesis, which is crucial in inflammation, but its role in nonalcoholic steatohepatitis (NASH) remains unclear. The aim of this study was to analyze RUNX1 mRNA hepatic and jejunal abundance in women with morbid obesity (MO) and NAFLD. RUNX1, lipid metabolism-related genes, and TLRs in women with MO and normal liver (NL, n = 28), NAFLD (n = 41) (simple steatosis (SS, n = 24), or NASH (n = 17)) were analyzed by RT-qPCR. The RUNX1 hepatic expression was higher in SS than in NL or NASH, as likewise confirmed by immunohistochemistry. An increased expression of hepatic FAS was found in NAFLD. Hepatic RUNX1 correlated positively with FAS. There were no significant differences in the jejunum RUNX1 expressions in the different groups. Jejunal FXR expression was lower in NASH than in NL, while the TLR9 expression increased as NAFLD progressed. Jejunal RUNX1 correlated positively with jejunal PPARγ, TLR4, and TLR5. In summary, the hepatic expression of RUNX1 seems to be involved in the first steps of the NAFLD process; however, in NASH, it seems to be downregulated. Our findings provide important insights into the role of RUNX1 in the context of NAFLD/NASH, suggesting a protective role.

Semi-Quantitative Ultrasonographic Evaluation of NAFLD

2020 ◽  
Vol 26 (32) ◽  
pp. 3915-3927 ◽  
Author(s):  
Stefano Ballestri ◽  
Claudio Tana ◽  
Maria Di Girolamo ◽  
Maria Cristina Fontana ◽  
Mariano Capitelli ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Imaging Techniques ◽  
Metabolic Complications ◽  
Nonalcoholic Fatty Liver ◽  
Non Invasive ◽  
Increased Risk ◽  
Risk Of Progression ◽  
Progressive Liver Disease

: Nonalcoholic fatty liver disease (NAFLD) embraces histopathological entities ranging from the relatively benign simple steatosis to the progressive form nonalcoholic steatohepatitis (NASH), which is associated with fibrosis and an increased risk of progression to cirrhosis and hepatocellular carcinoma. NAFLD is the most common liver disease and is associated with extrahepatic comorbidities including a major cardiovascular disease burden. : The non-invasive diagnosis of NAFLD and the identification of subjects at risk of progressive liver disease and cardio-metabolic complications are key in implementing personalized treatment schedules and follow-up strategies. : In this review, we highlight the potential role of ultrasound semiquantitative scores for detecting and assessing steatosis severity, progression of NAFLD, and cardio-metabolic risk. : Ultrasonographic scores of fatty liver severity act as sensors of cardio-metabolic health and may assist in selecting patients to submit to second-line non-invasive imaging techniques and/or liver biopsy.

scholarly journals Role of FXR in Bile Acid and Metabolic Homeostasis in NASH: Pathogenetic Concepts and Therapeutic Opportunities

2021 ◽  
Author(s):  
Richard Radun ◽  
Michael Trauner
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Enterohepatic Circulation ◽  
Therapeutic Potential ◽  
Farnesoid X Receptor ◽  
Metabolic Homeostasis ◽  
Nonalcoholic Fatty Liver ◽  
Metabolic Dysregulation ◽  
Attractive Therapeutic Target

AbstractNonalcoholic fatty liver disease (NAFLD) has become the most prevalent cause of liver disease, increasingly contributing to the burden of liver transplantation. In search for effective treatments, novel strategies addressing metabolic dysregulation, inflammation, and fibrosis are continuously emerging. Disturbed bile acid (BA) homeostasis and microcholestasis via hepatocellular retention of potentially toxic BAs may be an underappreciated factor in the pathogenesis of NAFLD and nonalcoholic steatohepatitis (NASH) as its progressive variant. In addition to their detergent properties, BAs act as signaling molecules regulating cellular homeostasis through interaction with BA receptors such as the Farnesoid X receptor (FXR). Apart from being a key regulator of BA metabolism and enterohepatic circulation, FXR regulates metabolic homeostasis and has immune-modulatory effects, making it an attractive therapeutic target in NAFLD/NASH. In this review, the molecular basis and therapeutic potential of targeting FXR with a specific focus on restoring BA and metabolic homeostasis in NASH is summarized.

scholarly journals Clinical characteristics and risk factors of nonalcoholic fatty liver disease in children with obesity

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Luting Peng ◽  
Su Wu ◽  
Nan Zhou ◽  
Shanliang Zhu ◽  
Qianqi Liu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Body Mass Index ◽  
Liver Disease ◽  
Fatty Liver Disease ◽  
Liver Enzymes ◽  
Early Stage ◽  
Prevention Strategies ◽  
Nonalcoholic Fatty Liver ◽  
Nash Group

Abstract Background With the increasing number of children with obesity worldwide, nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease among children. It is necessary to recognize the risk factors of NAFLD for prevention in childhood since NAFLD is asymptomatic in the early stage. Objectives. The objective of this study was to investigate possible risk factors of NAFLD in children with obesity, providing evidence for monitoring and prevention strategies at an early stage for obese children with NAFLD. Methods Data were collected from 428 children and adolescents aged 6-16 years recruited from the Children’s Hospital at Nanjing Medical University from September 2015 to April 2018 and analyzed. Based on a combination of ultrasound results and alanine transaminase levels, subjects were divided into three groups: simple obesity (SOB), simple steatosis (SS), and nonalcoholic fatty hepatitis (NASH). Blood biochemical examination included glucose, insulin, uric acid, lipid profile and liver enzymes. Results Among 428 children with obesity, 235 (54.9%) had SS and 45 (10.5%) had NASH. Body mass index, body mass index standard deviation score (BMI-SDS), waist circumference, body fat, liver enzymes, uric acid and HOMA-IR level were significantly higher in the NASH group than in the SS and SOB groups (p < 0.001). 53.3% of the SS group and 49.8% of the NASH group had metabolic syndrome, significantly more than in the SOB group (19.6%, p < 0.001). After adjustment for confounding factors, logistic regression models revealed that NASH was associated with BMI-SDS ≥ 3, gender, hyperuricemia and insulin resistance. Conclusions The prevalence of NASH in children with obesity is closely related to high BMI-SDS, gender, insulin resistance and hyperuricemia. These findings provide evidence that monitoring risk factors of childhood obesity can assist in developing prevention strategies for liver disease at an early stage.

scholarly journals Overview of Non-Alcoholic Fatty Liver Disease (NAFLD) and the Role of Sugary Food Consumption and Other Dietary Components in Its Development

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1442
Author(s):  
Pau Vancells Lujan ◽  
Esther Viñas Esmel ◽  
Emilio Sacanella Meseguer
Keyword(s):  
Clinical Trials ◽  
Liver Disease ◽  
Critical Role ◽  
Dietary Treatment ◽  
Dietary Interventions ◽  
Lifestyle Modifications ◽  
Alcoholic Fatty Liver ◽  
Effective Form ◽  
Unhealthy Diet

NAFLD is the world’s most common chronic liver disease, and its increasing prevalence parallels the global rise in diabetes and obesity. It is characterised by fat accumulation in the liver evolving to non-alcoholic steatohepatitis (NASH), an inflammatory subtype that can lead to liver fibrosis and cirrhosis. Currently, there is no effective pharmacotherapeutic treatment for NAFLD. Treatment is therefore based on lifestyle modifications including changes to diet and exercise, although it is unclear what the most effective form of intervention is. The aim of this review, then, is to discuss the role of specific nutrients and the effects of different dietary interventions on NAFLD. It is well established that an unhealthy diet rich in calories, sugars, and saturated fats and low in polyunsaturated fatty acids, fibre, and micronutrients plays a critical role in the development and progression of this disease. However, few clinical trials have evaluated the effects of nutrition interventions on NAFLD. We, therefore, summarise what is currently known about the effects of macronutrients, foods, and dietary patterns on NAFLD prevention and treatment. Most current guidelines recommend low-calorie, plant-based diets, such as the Mediterranean diet, as the most effective dietary pattern to treat NAFLD. More clinical trials are required, however, to identify the best evidence-based dietary treatment approach.

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