Search

Dietary fat composition is closely associated with the pathological development of alcoholic liver disease (ALD). Fat enriched with saturated fatty acids protects whereas with polyunsaturated fatty acids aggravates alcohol-induced liver injury. However, limited study has addressed how monounsaturated fatty acids (MUFAs) determines the pathological process of ALD. Our study was conducted to evaluate the effect of MUFAs-enriched-camellia seed oil (CSO) on alcohol-induced liver injury. The ALD model was established by feeding C57BL/6 mice with Lieber-DeCarli diet, and with either CSO or polyunsaturated fatty acids (PUFAs)-enriched-corn oil (CO) as fat source. After 4-week-intervention, CSO-feed rescued alcohol-induced liver injury compared to CO-feed, evidenced by measurements of plasma ALT activity, H&E stain, and hepatic cleaved-Caspase-3 expression. Besides, CSO-feed alleviated alcohol-induced oxidative stress, associated with NRF2 and Hif-1α expressions improvement. The reduction of F4/80 immunostaining and the decreased expressions of hepatic TNF-α and IL-6 suggested CSO-feed improved alcohol-induced inflammation. The mechanistic analysis showed that the inhibition of ASK1 and MAPKs might contribute to CSO-protected liver injury. Notably, we observed CSO-feed relieved the gut microbiota disturbance with the decreased Firmicutes and Turicibater, and the increased Bacteroidota, Alloprevotella, and Bacteroides, and reduced circulatory endotoxin level and lipolysis of adipose tissue, which are the known pathogenic factors in alcohol-induced liver injury. Unexpectedly, CSO induced more hepatic steatosis than CO-feed. In conclusion, CSO attenuated chronic alcohol consumption-induced liver injury but enhanced hepatic steatosis. CSO could be a potential dietary choice for alcoholic individuals with liver injury.

Background: Alcoholic liver disease (ALD) caused by chronic ethanol overconsumption is a common type of liver disease with a severe mortality burden throughout the world. The pathogenesis of ALD is complex, and no effective clinical treatment for the disease has advanced so far. Prolonged alcohol abstinence is the most effective therapy to attenuate the clinical course of ALD and even reverse liver damage. However, the molecular mechanisms involved in alcohol abstinence-improved recovery from alcoholic fatty liver remain unclear. This study aims to systematically evaluate the beneficial effect of alcohol abstinence on pathological changes in ALD.Methods: Using the Lieber-DeCarli mouse model of ALD, we analysed whether 1-week alcohol withdrawal reversed alcohol-induced detrimental alterations, including oxidative stress, liver injury, lipids metabolism, and hepatic inflammation, by detecting biomarkers and potential targets.Results: Alcohol withdrawal ameliorated alcohol-induced hepatic steatosis by improving liver lipid metabolism reprogramming via upregulating phosphorylated 5′-AMP -activated protein kinase (p-AMPK), peroxisome proliferator-activated receptor-α (PPAR-α), and carnitine palmitoyltransferase-1 (CPT-1), and downregulating fatty acid synthase (FAS) and diacylglycerol acyltransferase-2 (DGAT-2). The activities of antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxidase (GSH-px), were significantly enhanced by alcohol withdrawal. Importantly, the abstinence recovered alcohol-fed induced liver injury, as evidenced by the improvements in haematoxylin and eosin (H&E) staining, plasma alanine aminotransferase (ALT) levels, and liver weight/body weight ratio. Alcohol-stimulated toll-like receptor 4/mitogen-activated protein kinases (TLR4/MAPKs) were significantly reversed by alcohol withdrawal, which might mechanistically contribute to the amelioration of liver injury. Accordingly, the hepatic inflammatory factor represented by tumour necrosis factor-alpha (TNF-α) was improved by alcohol abstinence.Conclusion: In summary, we reported that alcohol withdrawal effectively restored hepatic lipid metabolism and reversed liver injury and inflammation by improving metabolism reprogramming. These findings enhanced our understanding of the biological mechanisms involved in the beneficial role of alcohol abstinence as an effective treatment for ALD.

Background and Aim: The worldwide prevalence of alcoholic liver disease (ALD) due to escalating alcohol consumption has presented an unprecedented pressure on human health. A few studies have determined long non-coding RNAs (lncRNAs) involved in the pathogenesis of liver diseases. However, the roles of lncRNAs in ALD development is still poorly understood.Methods: An ALD mouse model was established and confirmed. Expression profiles of lncRNAs were obtained by whole transcriptome sequencing. The altered lncRNAs in ALD mice were further verified by qRT-PCR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to enrich the functions of these lncRNAs. In combination with miRNA and mRNA profiles, we constructed concise endogenous RNA (ceRNA) networks. The function of the most up/downregulated lnRNA was further verified and investigated in both ALD model and AML-12 cells.Results: Totally, five downregulated lncRNAs were obtained and verified in ALD mice. The GO term and KEGG pathway analyses revealed that the identified lncRNAs were associated with alcohol-induced hepatic oxidative damage, cellular inflammation, and lipid metabolism. Combination the differentially modulated miRNAs and mRNAs with ceRNA network analysis, we constructed five ceRNA networks and obtained 30 miRNAs and 25 mRNAs that may participate in ALD. Further, we verified and investigate the function of the most downregulated lnc_1700023H06Rik. Depletion lnc_1700023H06Rik reduced genes encoding for lipid metabolism, especially mRNA Acat2 (ENSMUST00000159697) and Pgrmc2 (ENSMUST00000058578) both in vivo and in vitro. Knocking down lnc_1700023H06Rik induced triglyceride accumulation and lactate dehydrogenase leakage in AML12 cells, consisting with that in alcohol-treated cells.Conclusion: The five remarkably downregulated lncRNAs in ALD mouse model were identified as novel biomarkers, highlighting the key role of lncRNAs in the development of ALD. The effect of lnc_1700023H06Rik plays a pivotal role in lipid deposition and its pathological pathway in ALD needs further investigation.