Faculty Opinions recommendation of Comparison of gene expression patterns between mouse models of nonalcoholic fatty liver disease and liver tissues from patients.

2017 ◽  
Author(s):  
Mark Gorrell
Keyword(s):  
Gene Expression ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Mouse Models ◽  
Fatty Liver Disease ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Nonalcoholic Fatty Liver ◽  
Liver Tissues

CREBH knockout accelerates hepatic fibrosis in mouse models of diet-induced nonalcoholic fatty liver disease

Life Sciences ◽  
2020 ◽  
Vol 254 ◽  
pp. 117795 ◽  
Author(s):  
Guixin Li ◽  
Junli Zhang ◽  
Qianqian Jiang ◽  
Beibei Liu ◽  
Keshu Xu
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Hepatic Fibrosis ◽  
Mouse Models ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver

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.

scholarly journals Liver Proliferation Is an Essential Driver of Fibrosis in Mouse Models of Nonalcoholic Fatty Liver Disease

2019 ◽  
Vol 3 (8) ◽  
pp. 1036-1049 ◽  
Author(s):  
Ashley Cast ◽  
Meenasri Kumbaji ◽  
Amber D'Souza ◽  
Katherine Rodriguez ◽  
Anita Gupta ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Mouse Models ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver ◽  
Liver Proliferation

scholarly journals Gene Expression and DNA Methylation Alterations in the Glycine N-Methyltransferase Gene in Diet-Induced Nonalcoholic Fatty Liver Disease-Associated Carcinogenesis

2019 ◽  
Vol 170 (2) ◽  
pp. 273-282 ◽  
Author(s):  
Barbara Borowa-Mazgaj ◽  
Aline de Conti ◽  
Volodymyr Tryndyak ◽  
Colleen R Steward ◽  
Leandro Jimenez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Animal Model ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
The United States ◽  
Down Regulation ◽  
Nonalcoholic Fatty Liver

Abstract Nonalcoholic fatty liver disease (NAFLD) is becoming a major etiological risk factor for hepatocellular carcinoma (HCC) in the United States and other Western countries. In this study, we investigated the role of gene-specific promoter cytosine DNA methylation and gene expression alterations in the development of NAFLD-associated HCC in mice using (1) a diet-induced animal model of NAFLD, (2) a Stelic Animal Model of nonalcoholic steatohepatitis-derived HCC, and (3) a choline- and folate-deficient (CFD) diet (CFD model). We found that the development of NAFLD and its progression to HCC was characterized by down-regulation of glycine N-methyltransferase (Gnmt) and this was mediated by progressive Gnmt promoter cytosine DNA hypermethylation. Using a panel of genetically diverse inbred mice, we observed that Gnmt down-regulation was an early event in the pathogenesis of NAFLD and correlated with the extent of the NAFLD-like liver injury. Reduced GNMT expression was also found in human HCC tissue and liver cancer cell lines. In in vitro experiments, we demonstrated that one of the consequences of GNMT inhibition was an increase in genome methylation facilitated by an elevated level of S-adenosyl-L-methionine. Overall, our findings suggest that reduced Gnmt expression caused by promoter hypermethylation is one of the key molecular events in the development of NAFLD-derived HCC and that assessing Gnmt methylation level may be useful for disease stratification.

scholarly journals Insights into the evolving role of the gut microbiome in nonalcoholic fatty liver disease: rationale and prospects for therapeutic intervention

2019 ◽  
Vol 12 ◽  
pp. 175628481985847 ◽  
Author(s):  
Marialena Mouzaki ◽  
Rohit Loomba
Keyword(s):  
Gene Expression ◽  
Liver Disease ◽  
Energy Expenditure ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Intestinal Microbiome ◽  
Significant Morbidity ◽  
Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD) is diagnosed across the age spectrum and contributes to significant morbidity and mortality. The pathophysiology of NAFLD is not entirely understood; however, recent evidence has implicated the intestinal microbiome. Through the effects on host appetite, energy expenditure, digestion, gene expression, intestinal permeability, as well as immune activation, a dysbiotic microbiome can contribute to the development and progression of the hepatocellular steatosis, inflammation and fibrosis seen in the context of NAFLD. As such, intestinal microbiota and products of their metabolism have been targeted as treatment approaches for NAFLD.

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