scholarly journals New Perspectives on Genetic Prediction for Pediatric Metabolic Associated Fatty Liver Disease

2020 ◽  
Vol 8 ◽  
Author(s):  
Yu-Cheng Lin ◽  
Chi-Chien Wu ◽  
Yen-Hsuan Ni
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Human Genetics ◽  
Obese Subject ◽  
Public Health Issue ◽  
Racial Groups ◽  
Personalized Care ◽  
Genetic And Environmental Factors

Non-alcoholic or recently re-defined metabolic associated fatty liver disease (MAFLD), a spectrum of progressive hepatic disease, has become a public health issue in obese children and adolescents. MAFLD is a complex metabolic disease strongly associated with obesity and insulin resistance. It is not known why not every obese subject will develop MAFLD. Different ethnic/racial groups display differences in MAFLD prevalence, indicating genetic factor plays a role. In the past two decades, sequence variations in genetic loci, including PNPLA3, TM6SF2, GCKR, MBOAT7, HSD17B13, etc. have been shown to confer susceptibility to MAFLD in children and adults. This review article provides an updated viewpoint of genetic predictors related to pediatric MAFLD. We discuss whether these susceptible genes can be clinically used for risk stratification and personalized care. Understanding human genetics and molecular mechanisms can give important information not only for prediction of risk but also on how to design drugs. In view of current epidemic of MAFLD worldwide, it is necessary to identify which children with MAFLD progress rapidly and need earlier intervention. In the future, a comprehensive analysis of individualized genetic and environmental factors may help assess the risk of children with MAFLD and personalize their treatment.

Molecular mechanisms of non-alcoholic fatty liver disease development

2021 ◽  
Vol 24 (4) ◽  
pp. 120
Author(s):  
T.S. Sall ◽  
E.S. Shcherbakova ◽  
S.I. Sitkin ◽  
T.Ya. Vakhitov ◽  
I.G. Bakulin ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Disease Development ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

scholarly journals Sex Dimorphism of Nonalcoholic Fatty Liver Disease (NAFLD) in Pparg-Null Mice

2021 ◽  
Vol 22 (18) ◽  
pp. 9969
Author(s):  
Mariano Schiffrin ◽  
Carine Winkler ◽  
Laure Quignodon ◽  
Aurélien Naldi ◽  
Martin Trötzmüller ◽  
...  
Keyword(s):  
Gene Expression ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Liver Steatosis ◽  
Whole Body ◽  
Sex Dimorphism ◽  
Nonalcoholic Fatty Liver

Men with nonalcoholic fatty liver disease (NAFLD) are more exposed to nonalcoholic steatohepatitis (NASH) and liver fibrosis than women. However, the underlying molecular mechanisms of NALFD sex dimorphism are unclear. We combined gene expression, histological and lipidomic analyses to systematically compare male and female liver steatosis. We characterized hepatosteatosis in three independent mouse models of NAFLD, ob/ob and lipodystrophic fat-specific (PpargFΔ/Δ) and whole-body PPARγ-null (PpargΔ/Δ) mice. We identified a clear sex dimorphism occurring only in PpargΔ/Δ mice, with females showing macro- and microvesicular hepatosteatosis throughout their entire life, while males had fewer lipid droplets starting from 20 weeks. This sex dimorphism in hepatosteatosis was lost in gonadectomized PpargΔ/Δ mice. Lipidomics revealed hepatic accumulation of short and highly saturated TGs in females, while TGs were enriched in long and unsaturated hydrocarbon chains in males. Strikingly, sex-biased genes were particularly perturbed in both sexes, affecting lipid metabolism, drug metabolism, inflammatory and cellular stress response pathways. Most importantly, we found that the expression of key sex-biased genes was severely affected in all the NAFLD models we tested. Thus, hepatosteatosis strongly affects hepatic sex-biased gene expression. With NAFLD increasing in prevalence, this emphasizes the urgent need to specifically address the consequences of this deregulation in humans.

Is liver fat detrimental to vessels?: intersections in the pathogenesis of NAFLD and atherosclerosis

2008 ◽  
Vol 115 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Paola Loria ◽  
Amedeo Lonardo ◽  
Giovanni Targher
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Liver Fat ◽  
Cvd Risk ◽  
Alcoholic Fatty Liver ◽  
Insulin Resistant ◽  
Major Player

NAFLD (non-alcoholic fatty liver disease) encompasses the spectrum of fatty liver disease in insulin-resistant individuals who often display T2DM (Type 2 diabetes mellitus) and obesity. The present review highlights the pathophysiological basis and clinical evidence for a possible causal linkage between NAFLD and CVD (cardiovascular disease). The role of traditional and non-traditional CVD risk factors in the pathophysiology of NAFLD is considered in the first part of the review, with the basic science shared by atherogenesis and hepatic steatogenesis discussed in depth in the second part. In conclusion, NAFLD is not an innocent bystander, but a major player in the development and progression of CVD. NAFLD and CVD also share similar molecular mechanisms and targeted treatment strategies. On the research side, studies should focus on interventions aimed at restoring energy homoeostasis in lipotoxic tissues and at improving hepatic (micro)vascular blood supply.

Potential Natural Compounds for the Prevention and Treatment of Nonalcoholic Fatty Liver Disease: A Review on Molecular Mechanisms

2021 ◽  
Vol 15 ◽  
Author(s):  
Cheng Ma ◽  
Cheng Wang ◽  
Yafang Zhang ◽  
Honglin Zhou ◽  
Yunxia Li
Keyword(s):  
Liver Disease ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Natural Compounds ◽  
Nonalcoholic Fatty Liver ◽  
Prevention And Treatment

Background: Nonalcoholic fatty liver disease (NAFLD) is a kind of metabolic stress-induced liver injury closely related to insulin resistance and genetic susceptibility, and there is no specific drug for its clinical treatment currently. In recent years, a large amount of literature has reported that many natural compounds extracted from traditional Chinese medicine (TCM) can improve NAFLD through various mechanisms. According to the latest reports, some emerging natural compounds have shown great potential to improve NAFLD but are seldom used clinically due to the lacking special research. Purpose: This paper aims to summarize the molecular mechanisms of the potential natural compounds on improving NAFLD, thus providing a direction and basis for further research on the pathogenesis of NAFLD and the development of effective drugs for the prevention and treatment of NAFLD. Methods: By searching various online databases, such as Web of Science, SciFinder, PubMed, and CNKI, NAFLD and these natural compounds were used as the keywords for detailed literature retrieval. Results: The pathogenesis of NAFLD and the molecular mechanisms of the potential natural compounds on improving NAFLD have been reviewed. Conclusion: Many natural compounds from traditional Chinese medicine have a good prospect in the treatment of NAFLD, which can serve as a direction for the development of anti-NAFLD drugs in the future.

scholarly journals A Role for Gut Microbiome Fermentative Pathways in Fatty Liver Disease Progression

2020 ◽  
Vol 9 (5) ◽  
pp. 1369 ◽  
Author(s):  
Paula Iruzubieta ◽  
Juan M. Medina ◽  
Raúl Fernández-López ◽  
Javier Crespo ◽  
Fernando de la Cruz
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Disease Progression ◽  
Gut Microbiome ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Alcohol Fermentation ◽  
Alcoholic Fatty Liver ◽  
Liver Disease Progression ◽  
The Impact

Non-alcoholic fatty liver disease (NAFLD) is a multifactorial disease in which environmental and genetic factors are involved. Although the molecular mechanisms involved in NAFLD onset and progression are not completely understood, the gut microbiome (GM) is thought to play a key role in the process, influencing multiple physiological functions. GM alterations in diversity and composition directly impact disease states with an inflammatory course, such as non-alcoholic steatohepatitis (NASH). However, how the GM influences liver disease susceptibility is largely unknown. Similarly, the impact of strategies targeting the GM for the treatment of NASH remains to be evaluated. This review provides a broad insight into the role of gut microbiota in NASH pathogenesis, as a diagnostic tool, and as a therapeutic target in this liver disease. We highlight the idea that the balance in metabolic fermentations can be key in maintaining liver homeostasis. We propose that an overabundance of alcohol-fermentation pathways in the GM may outcompete healthier, acid-producing members of the microbiota. In this way, GM ecology may precipitate a self-sustaining vicious cycle, boosting liver disease progression.

scholarly journals Sijunzi, Lizhong, and Fuzilizhong Decoction Alleviate Nonalcoholic Fatty Liver Disease through Activation of PPAR Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Jiayao Yang ◽  
Dongqing Tao ◽  
Wei Ma ◽  
Song Liu ◽  
Yan Liao ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Peroxisome Proliferator ◽  
High Fat ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nonalcoholic Fatty Liver ◽  
Chinese Herbal

Objective. Sijunzi, Lizhong, and Fuzilizhong decoction were traditional Chinese classic formulations, which are widely used in clinical treatment, and the underlying mechanism is unclear. In this study, we aim to investigate the molecular mechanisms underlying the protective effects of Sijunzi, Lizhong, and Fuzilizhong on nonalcoholic fatty liver disease (NAFLD). Methods. Male Wistar rats were fed a high-fat diet for four weeks to induce NAFLD and were thereafter administered Sijunzi (8 g/kg/d), Lizhong (10 g/kg/d), or Fuzilizhong (10 g/kg/d) by gavage for four weeks. Hepatic damage, lipid accumulation, inflammation, autophagy, and peroxisome proliferator-activated receptor-α signaling were evaluated. Results. The high-fat diet-fed rats showed typical symptoms of NAFLD, including elevated levels of hepatic damage indicators, increased hepatic lipid deposition and fibrosis, severe liver inflammation, and prominent autophagy. Upon administration of Sijunzi, Lizhong, and Fuzilizhong, liver health was improved remarkably, along with ameliorated symptoms of NAFLD. In addition, NAFLD-suppressed peroxisome proliferator-activated receptor-α signaling was reactivated after treatment with the three types of decoctions. Conclusions. The results collectively signify the effective therapeutic and protective functions of Sijunzi, Lizhong, and Fuzilizhong against NAFLD and demonstrate the potential of Chinese herbal medication in mitigating the symptoms of liver diseases. Novelty of the Work. Traditional Chinese herbal medicine has been used for centuries to treat various diseases, but the molecular mechanisms of individual ingredients have rarely been studied. The novelty of our work lies in elucidating the specific signaling pathways involved in the control of NAFLD using three common Chinese herbal decoctions. We suggest that natural herbal formulations can be effective therapeutic agents to combat against NAFLD.

scholarly journals Acupuncture on ST36, CV4 and KI1 Suppresses the Progression of Methionine- and Choline-Deficient Diet-Induced Nonalcoholic Fatty Liver Disease in Mice

Metabolites ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 299 ◽  
Author(s):  
Xiangjin Meng ◽  
Xin Guo ◽  
Jing Zhang ◽  
Junji Moriya ◽  
Junji Kobayashi ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Acupuncture Treatment ◽  
Lipid Analysis ◽  
Altered Expression ◽  
Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide, and its treatment remain a constant challenge. A number of clinical trials have shown that acupuncture treatment has beneficial effects for patients with NAFLD, but the molecular mechanisms underlying its action are still largely unknown. In this study, we established a mouse model of NAFLD by administering a methionine- and choline-deficient (MCD) diet and selected three acupoints (ST36, CV4, and KI1) or nonacupoints (sham) for needling. We then investigated the effects of acupuncture treatment on the progression of NAFLD and the underlying mechanisms. After two weeks of acupuncture treatment, the liver in the needling-nonapcupoint group (NG) mice appeared pale and yellowish in color, while that in the needling-acupoint group (AG) showed a bright red color. Histologically, fewer lipid droplets and inflammatory foci were observed in the AG liver than in the NG liver. Furthermore, the expression of proinflammatory signaling factors was significantly downregulated in the AG liver. A lipid analysis showed that the levels of triglyceride (TG) and free fatty acid (FFA) were lower in the AG liver than in the NG liver, with an altered expression of lipid metabolism-related factors as well. Moreover, the numbers of 8-hydroxy-2′-deoxyguanosine (8-OHdG)-positive hepatocytes and levels of hepatic thiobarbituric acid reactive substances (TBARS) were significantly lower in AG mice than in NG mice. In line with these results, a higher expressions of antioxidant factors was found in the AG liver than in the NG liver. Our results indicate that acupuncture repressed the progression of NAFLD by inhibiting inflammatory reactions, reducing oxidative stress, and promoting lipid metabolism of hepatocytes, suggesting that this approach might be an important complementary treatment for NAFLD.

scholarly journals Noncoding RNAs in Nonalcoholic Fatty Liver Disease: Potential Diagnosis and Prognosis Biomarkers

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Olfa Khalifa ◽  
Khaoula Errafii ◽  
Nayla S. Al-Akl ◽  
Abdelilah Arredouani
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Noncoding Rnas ◽  
Epigenetic Factors ◽  
Nonalcoholic Fatty Liver ◽  
Regulatory Pathways ◽  
Hepatocellular Damage

Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease worldwide in part due to the concomitant obesity pandemic and insulin resistance (IR). It is increasingly becoming evident that NAFLD is a disease affecting numerous extrahepatic vital organs and regulatory pathways. The molecular mechanisms underlying the nonalcoholic steatosis formation are poorly understood, and little information is available on the pathways that are responsible for the progressive hepatocellular damage that follows lipid accumulation. Recently, much research has focused on the identification of the epigenetic modifications that contribute to NAFLD pathogenesis. Noncoding RNAs (ncRNAs) are one of such epigenetic factors that could be implicated in the NAFLD development and progression. In this review, we summarize the current knowledge of the genetic and epigenetic factors potentially underlying the disease. Particular emphasis will be put on the contribution of microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) to the pathophysiology of NAFLD as well as their potential use as therapeutic targets or as markers for the prediction and the progression of the disease.

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