Dataset Information

Long chain non-coding RNA-EN_181 potentially contributes to the protective role of N-acetylcysteine against non-alcoholic fatty liver disease in mice

ABSTRACT: Background: N-acetylcysteine (NAC), a scavenger of free radicals, possesses strong capability to improve high fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in mice. However, the underlying mechanism(s) of NAC-ameliorated NAFLD are still not fully illustrated. This study was designed to clarify the involvement of long chain non-coding RNAs (lncRNAs) in the beneficial effects of NAC on NAFLD in HFD-induced obese mice. Methods: C57BL/6J mice were arranged into normal fat diet (10% energy from fat), HFD (45% energy from fat), and HFD plus NAC (2 g/L in drinking water) groups, respectively. After 14-week intervention, the role of NAC was determined by immunohistochemistry and biochemical indexes in both plasma and liver. The profiles of hepatic lncRNAs were analyzed by whole transcriptome sequencing, and were further verified by quantitative real-time polymerase chain reaction (qRT-PCR). Meanwhile, the gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses were carried out to identify the functions of candidate lncRNAs. Furthermore, lncRNA-related ceRNA network was constructed in combination with miRNA and mRNA profiles by Cytoscape software. Results: NAC treatment obviously rescued the deleterious alterations induced by HFD, including body and liver weight, hepatic triglyceride (TG), plasma alanine aminotransferase (ALT), plasma aspartate transaminase (AST), and liver histomorphology (H&E and Oil red O staining). Through whole transcriptome sequencing technology, 52167 (50758 known and 1409 novel) lncRNAs were detectable in liver samples. Our data revealed that the expressions of 175 lncRNAs were significantly changed by HFD but reversed by NAC treatment through cross-comparison. Among those lncRNAs, 5 lncRNAs, including lncRNA-NONMMUT148902.1 (NO_902.1), lncRNA-XR_001781798.1 (XR_798.1), lncRNA-NONMMUT141720.1 (NO_720.1), lncRNA-XR_869907.1 (XR_907.1), and lncRNA-ENSMUST00000132181 (EN_181), were selected based on the absolute value of log2 fold change (FC) being greater than 4, P-value ＜ 0.01, and P-adjust ＜ 0.01. Further qRT-PCR identified that lncRNA-NO_902.1, lncRNA-XR_798.1, and lncRNA-EN_181 were dramatically decreased by HFD while rescued by NAC treatment, consistent with the RNA-sequencing. Finally, we further screened and constructed a ceRNA network, including lncRNA-EN_181, 3 miRNAs, and 13 mRNAs, which was associated with the beneficial role of NAC in NAFLD. Conclusions: This study identified for the first time that lncRNA-EN_181 might be a potential target in NAC-ameliorated NAFLD. The finding enhanced our understanding of biological mechanisms in the beneficial role of NAC.

ORGANISM(S): Mus musculus

PROVIDER: GSE188128 | GEO | 2024/07/31

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Objective: Nonalcoholic fatty liver disease (NAFLD) is linked to obesity and diabetes, suggesting an important role of adipose tissue in the pathogenesis of NAFLD. Here we aim to investigate the interaction between adipose tissue and liver in NAFLD, and identify potential early plasma markers that predict NASH. Research Design and Methods: C57Bl/6 mice were chronically fed a high fat diet to induce NAFLD and compared with mice fed low fat diet. Extensive histological and phenotypical analyses coupled with a time-course study of plasma proteins using multiplex assay was performed. Results: Mice exhibited pronounced heterogeneity in liver histological scoring, leading to classification into 4 subgroups: LF-low (LFL) responders displaying normal liver morphology, LF-high (LFH) responders showing benign hepatic steatosis, HF-low (HFL) responders displaying pre-NASH with macrovesicular lipid droplets, and HF-high (HFH) responders exhibiting overt NASH characterized by ballooning of hepatocytes, presence of Mallory bodies, and activated inflammatory cells. Compared to HFL responders, HFH mice gained weight more rapidly and exhibited adipose tissue dysfunction characterized by decreased final fat mass, enhanced macrophage infiltration and inflammation, and adipose tissue remodelling. Plasma haptoglobin, IL-1β, TIMP-1, adiponectin and leptin were significantly changed in HFH mice. Multivariate analysis indicated that in addition to leptin, plasma CRP, haptoglobin, eotaxin and MIP-1α early in the intervention were positively associated with liver triglycerides. Intermediate prognostic markers of liver triglycerides included IL-18, IL-1β, MIP-1γ and MIP-2, whereas insulin, TIMP-1, GCP-2 and MPO emerged as late markers. Conclusions: Our data support the existence of a tight relationship between adipose tissue dysfunction and NASH pathogenesis and point to several novel potential predictive biomarkers for NASH. Keywords: Expression profiling by array Male wildtype C57Bl/6 mice were fed LFD or HFD for 21 weeks. Mice were divided into 4 groups based on liver histology.

Project description:The pathological progression of nonalcoholic fatty liver disease (NAFLD) is driven by multiple factors, and nonalcoholic steatohepatitis (NASH) represents its progressive form. In our previous studies, we found that bicyclol had beneficial effects on NAFLD/NASH. Here we aim to investigate the underlying molecular mechanisms of the bicyclol effect on NAFLD/NASH induced by high-fat diet (HFD) feeding. A mice model of NAFLD/NASH induced by HFD-feeding for 8 weeks was used. As a pretreatment, bicyclol (200 mg/kg) was given to mice by oral gavage twice daily. Hematoxylin and eosin (H&E) stains were processed to evaluate hepatic steatosis, and hepatic fibrous hyperplasia was assessed by Masson staining. Biochemistry analyses were used to measure serum aminotransferase, serum lipids, and lipids in liver tissues. Proteomics and bioinformatics analyses were performed to identify the signaling pathways and target proteins. The real-time RT-PCR and Western blot analyses were performed to verify the proteomics data. As a result, bicyclol had a markedly protective effect against NAFLD/NASH by suppressing the increase of serum aminotransferase, hepatic lipid accumulation and alleviating histopathological changes in liver tissues. Proteomics analyses showed that bicyclol remarkably restored major pathways related to immunological responses and metabolic processes altered by HFD feeding. Consistent with our previous results, bicyclol significantly inhibited inflammation and oxidative stress pathway related indexes (SAA1, GSTM1 and RDH11). Furthermore, the beneficial effects of bicyclol were closely associated with the signaling pathways of bile acid metabolism (NPC1, SLCOLA4 and UGT1A1), cytochrome P450-mediated metabolism (CYP2C54, CYP2C70 and CYP3A25), biological processes such as metal ion metabolism (Ceruloplasmin and Metallothionein-1), angiogenesis (ALDH1A1) and immunological responses (IFI204 and IFIT3). These findings suggested that bicyclol is a potential preventive agent for NAFLD/NASH by targeting multiple mechanisms in future clinical investigations.

Dataset Information

Long chain non-coding RNA-EN_181 potentially contributes to the protective role of N-acetylcysteine against non-alcoholic fatty liver disease in mice

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets