Unique features associated with hepatic oxidative DNA damage and DNA methylation in non-alcoholic fatty liver disease

2016 ◽  
Vol 31 (9) ◽  
pp. 1646-1653 ◽  
Author(s):  
Naoshi Nishida ◽  
Norihisa Yada ◽  
Satoru Hagiwara ◽  
Toshiharu Sakurai ◽  
Masayuki Kitano ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Dna Damage ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Oxidative Dna Damage ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

scholarly journals The DNA damage checkpoint protein ATM promotes hepatocellular apoptosis and fibrosis in a mouse model of non-alcoholic fatty liver disease

Cell Cycle ◽  
2012 ◽  
Vol 11 (10) ◽  
pp. 1918-1928 ◽  
Author(s):  
Erin K. Daugherity ◽  
Gabriel Balmus ◽  
Ahmed Al Saei ◽  
Elizabeth S. Moore ◽  
Delbert Abi Abdallah ◽  
...  
Keyword(s):  
Dna Damage ◽  
Liver Disease ◽  
Mouse Model ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Dna Damage Checkpoint ◽  
Alcoholic Fatty Liver ◽  
Checkpoint Protein ◽  
Hepatocellular Apoptosis ◽  
Alcoholic Fatty Liver Disease

scholarly journals Microbial Intervention as a Novel Target in Treatment of Non-Alcoholic Fatty Liver Disease Progression

2018 ◽  
Vol 51 (5) ◽  
pp. 2123-2135 ◽  
Author(s):  
Youlian Zhou ◽  
Tiying Zheng ◽  
Huiting Chen ◽  
Yongqiang Li ◽  
Hongli Huang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Liver Disease ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Serum Adiponectin ◽  
Promoter Regions ◽  
Alcoholic Fatty Liver ◽  
Probiotic Treatment ◽  
Alcoholic Fatty Liver Disease

Background/Aims: Emerging evidence suggests a close link between gut microbiota and non-alcoholic fatty liver disease (NAFLD). In this study, we aimed to investigate the association between gut microbiota and the DNA methylation of adiponectin (an adipocyte-specific adipocytokine) in rats, following diet-induced NAFLD. Methods: 50 male SD rats were randomly divided into five groups with or without a high fat diet (HFD), antibiotics, and probiotics, in order to establish an imbalanced gut microbiota and probiotic treatment model in NAFLD rats. After 13 weeks of treatment, blood, liver, and cecal tissue samples were collected. Serum lipids, liver function indexes by biochemical analyzers, and changes in liver pathology with hematoxylin-eosin (HE) and masson staining were detected. Furthermore, the serum adiponectin by enzyme-linked immunosorbent assay (ELISA) and liver adiponectin methylation levels in the promoter regions by pyrophosphate sequencing were determined. High throughput Illumina sequencing targeted microbial 16S genes, bioinformatics and statistical analysis identified cecal-associated gut microbiota. Results: HFD with antibiotic exposure showed the most severe steatohepatitis and a severe gut microbiota alteration. Reduced bacterial diversity was also seen and the abundances of Firmicutes, Lactobacillus, Cyanobacteria, Acidobacteria, Chlamydiae, Chlamydiales, Rubrobacteria, Verrucomicrobia, Blautia, Shewanella, Bacteroides, Bacteroides acidifaciens, and Bacteroides uniformis, were shown to be partly reversed by probiotic treatment. Decreased serum adiponectin levels and increased DNA methylation levels of adiponectin promoter regions were also markedly associated with the NAFLD progression during gut microbiota alteration. Conclusion: Our results suggested that both gut microbiota alteration and adiponectin variability may be drivers of NAFLD progression and that targeting the gut microbiota, such as via administration of a probiotic, may delay NAFLD progression via adiponectin.

scholarly journals Newborn and childhood differential DNA methylation and liver fat in school-age children

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Madelon L. Geurtsen ◽  
Vincent W. V. Jaddoe ◽  
Lucas A. Salas ◽  
Susana Santos ◽  
Janine F. Felix
Keyword(s):  
Dna Methylation ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Liver Fat ◽  
School Age Children ◽  
Alcoholic Fatty Liver ◽  
Fat Accumulation ◽  
Fat Fraction ◽  
Alcoholic Fatty Liver Disease

Abstract Background Non-alcoholic fatty liver disease is the most common chronic liver disease in children in western countries. Adverse early-life exposures are associated with higher liver fat percentages in children. Differential DNA methylation may underlie these associations. We aimed to identify differential DNA methylation in newborns and children associated with liver fat accumulation in childhood. We also examined whether DNA methylation at 22 cytosine-phosphate-guanine sites (CpGs) associated with adult non-alcoholic fatty liver disease is associated with liver fat in children. Within a population-based prospective cohort study, we analyzed epigenome-wide DNA methylation data of 785 newborns and 344 10-year-old children in relation to liver fat fraction at 10 years. DNA methylation was measured using the Infinium HumanMethylation450 BeadChip (Illumina). We measured liver fat fraction by Magnetic Resonance Imaging. Associations of single CpG DNA methylation at the two-time points with liver fat accumulation were analyzed using robust linear regression models. We also analyzed differentially methylation regions using the dmrff package. We looked-up associations of 22 known adult CpGs at both ages with liver fat at 10 years. Results The median liver fat fraction was 2.0% (95% range 1.3, 5.1). No single CpGs and no differentially methylated regions were associated with liver fat accumulation. None of the 22 known adult CpGs were associated with liver fat in children. Conclusions DNA methylation at birth and in childhood was not associated with liver fat accumulation in 10-year-old children in this study. This may be due to modest sample sizes or DNA methylation changes being a consequence rather than a determinant of liver fat.

scholarly journals Plasma DNA methylation: a potential biomarker for stratification of liver fibrosis in non-alcoholic fatty liver disease

Gut ◽  
2016 ◽  
Vol 66 (7) ◽  
pp. 1321-1328 ◽  
Author(s):  
Timothy Hardy ◽  
Mujdat Zeybel ◽  
Christopher P Day ◽  
Christian Dipper ◽  
Steven Masson ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Liver Disease ◽  
Liver Fibrosis ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Plasma Dna ◽  
Alcoholic Fatty Liver ◽  
Potential Biomarker ◽  
Alcoholic Fatty Liver Disease

scholarly journals The Co-occurrence of Chronic Hepatitis B and Fibrosis Is Associated With a Decrease in Hepatic Global DNA Methylation Levels in Patients With Non-alcoholic Fatty Liver Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
FangYuan Li ◽  
Qian Ou ◽  
ZhiWei Lai ◽  
LiuZhen Pu ◽  
XingYi Chen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Chronic Hepatitis ◽  
Liver Disease ◽  
Hepatitis B ◽  
Fatty Liver ◽  
Chronic Hepatitis B ◽  
Fatty Liver Disease ◽  
Global Dna Methylation ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Global DNA hypomethylation has been reported in patients with chronic hepatitis B (CHB) and non-alcoholic fatty-liver disease (NAFLD). However, the global DNA methylation profile of patients with concurrent NAFLD and CHB (NAFLD + CHB) is still unclear. We aimed to detect the hepatic global DNA methylation levels of NAFLD + CHB patients and assess the associated risk factors. Liver biopsies were collected from 55 NAFLD patients with or without CHB. The histological characteristics of the biopsy were then assessed. Hepatic global DNA methylation levels were quantified by fluorometric method. The hepatic global DNA methylation levels in NAFLD + CHB group were significantly lower than that in NAFLD group. Participants with fibrosis showed lower levels of hepatic global DNA methylation than those without fibrosis. Participants with both CHB and fibrosis had lower levels of hepatic global DNA methylation than those without either CHB or fibrosis. The co-occurrence of CHB and fibrosis was significantly associated with a reduction in global DNA methylation levels compared to the absence of both CHB and fibrosis. Our study suggests that patients with NAFLD + CHB exhibited lower levels of global DNA methylation than patients who had NAFLD alone. The co-occurrence of CHB and liver fibrosis in NAFLD patients was associated with a decrease in global DNA methylation levels.

scholarly journals Key features of the environment promoting liver cancer in the absence of cirrhosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marco Youssef William Zaki ◽  
Ahmed Khairallah Mahdi ◽  
Gillian Lucinda Patman ◽  
Anna Whitehead ◽  
João Pais Maurício ◽  
...  
Keyword(s):  
Dna Damage ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Liver Weight ◽  
Hepatocyte Proliferation ◽  
Alcoholic Fatty Liver ◽  
Key Features ◽  
Alcoholic Fatty Liver Disease ◽  
Lobular Inflammation

AbstractThe prevalence of obesity and non-alcoholic fatty liver disease (NAFLD) associated hepatocellular carcinoma (HCC) is rising, even in the absence of cirrhosis. We aimed to develop a murine model that would facilitate further understanding of NAFLD-HCC pathogenesis. A total of 144 C3H/He mice were fed either control or American lifestyle (ALIOS) diet, with or without interventions, for up to 48 weeks of age. Gross, liver histology, immunohistochemistry (IHC) and RNA-sequencing data were interpreted alongside human datasets. The ALIOS diet promoted obesity, elevated liver weight, impaired glucose tolerance, non-alcoholic fatty liver disease (NAFLD) and spontaneous HCC. Liver weight, fasting blood glucose, steatosis, lobular inflammation and lipogranulomas were associated with development of HCC, as were markers of hepatocyte proliferation and DNA damage. An antioxidant diminished cellular injury, fibrosis and DNA damage, but not lobular inflammation, lipogranulomas, proliferation and HCC development. An acquired CD44 phenotype in macrophages was associated with type 2 diabetes and NAFLD-HCC. In this diet induced NASH and HCC (DINAH) model, key features of obesity associated NAFLD-HCC have been reproduced, highlighting roles for hepatic steatosis and proliferation, with the acquisition of lobular inflammation and CD44 positive macrophages in the development of HCC—even in the absence of progressive injury and fibrosis.

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