Dataset Information

The nuclear and cytoplasmic roles of miR-320 in non-alcoholic fatty liver disease.

ABSTRACT:

Background

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder worldwide. Multiple metabolic disorders, such as hyperlipidemia, hyperglycemia, insulin resistance and obesity, have been reportedly associated with NAFLD, but little is known about the detailed mechanisms.

Methods and results

Here, we explored the effects of multiple metabolic disorders, especially hyperglycemia on lipid accumulation in liver using several well-established animal models. We found that liver lipid deposition was increased in both type 1 diabetes and high-fat diet (HFD) induced hyperlipidemia models, suggesting that either hyperglycemia or hyperlipidemia alone or together was able to trigger NAFLD. Moreover, we tested whether miR-320, a miRNA promoting lipid accumulation in heart revealed by our previous study, also participated in NAFLD. Though miR-320 treatment further increased liver lipid deposition in type 1 diabetes and HFD-feeding mice, it showed no effect in leptin-receptor deficient db/db mice. Interestingly, miR-320 affected different target genes in cytosol and nucleus, respectively, which collectively led to liver lipid overload.

Conclusions

Our findings illustrated the complex roles of miRNAs in subcellular fractions including nucleus and cytoplasm, which may lead to new insights into the mechanisms and treatment strategies for NAFLD in the future.

SUBMITTER: Zhan J

PROVIDER: S-EPMC11623971 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Publications

The nuclear and cytoplasmic roles of miR-320 in non-alcoholic fatty liver disease.

Zhan Jiabing J Lv Huizhen H Dai Beibei B Yuan Shuai S Fan Jiahui J Zhao Yanru Y Yin Zhongwei Z Wang Dao Wen DW Chen Chen C Li Huaping H

Aging 20201107 21

<h4>Background</h4>Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder worldwide. Multiple metabolic disorders, such as hyperlipidemia, hyperglycemia, insulin resistance and obesity, have been reportedly associated with NAFLD, but little is known about the detailed mechanisms.<h4>Methods and results</h4>Here, we explored the effects of multiple metabolic disorders, especially hyperglycemia on lipid accumulation in liver using several well-established animal models ...[more]

PMID: 33186123

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Project description:Background & Aims: Cirrhosis and liver cancer are potential outcomes of advanced nonalcoholic fatty liver disease (NAFLD). It is not clear what factors determine whether patients will develop advanced or mild NAFLD, limiting non-invasive diagnosis and treatment before clinical sequelae emerge. We investigated whether DNA methylation profiles can distinguish patients with mild disease from those with advanced NAFLD, and how these patterns are functionally related to hepatic gene expression. Methods: We collected frozen liver biopsies and clinical data from patients with biopsy-proven NAFLD (56 in the discovery cohort and 34 in the replication cohort). Samples were divided into groups based on histologic severity of fibrosis: F0?1 (mild) and F3?4 (advanced). DNA methylation profiles were determined and coupled with gene expression data from the same biopsies; differential methylation was validated in subsets of the discovery and replication cohorts. We then analyzed interactions between the methylome and transcriptome. Results: Clinical features did not differ between patients known to have mild or advanced fibrosis based on biopsy analysis. There were 69,247 differentially methylated CpG sites (76% hypomethylated, 24% hypermethylated) in patients with advanced vs mild NAFLD (P<.05). Methylation at FGFR2, MAT1A, and CASP1 was validated by bisulfite pyrosequencing and the findings were reproduced in the replication cohort. Methylation correlated with gene transcript levels for 7% of differentially methylated CpG sites, indicating that differential methylation contributes to differences in expression. In samples with advanced NAFLD, many tissue repair genes were hypomethylated and overexpressed, whereas genes in certain metabolic pathways, including 1-carbon metabolism, were hypermethylated and under-expressed. Conclusions: Functionally relevant differences in methylation can distinguish patients with advanced vs mild NAFLD. Altered methylation of genes that regulate processes such as steatohepatitis, fibrosis, and carcinogenesis indicate the role of DNA methylation in progression of NAFLD. Three technical replicates were included for quality control along with 35 mild NAFLD (33 unique samples) and 24 advanced NAFLD (23 unique sample). One sample per technical duplication was randomly included for a total of 56 NAFLD samples used for study.

Dataset Information

The nuclear and cytoplasmic roles of miR-320 in non-alcoholic fatty liver disease.

Background

Methods and results

Conclusions

Publications

The nuclear and cytoplasmic roles of miR-320 in non-alcoholic fatty liver disease.

Similar Datasets

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