Alcoholic fatty liver disease inhibited the co-expression of Fmo5 and PPARα to activate the NF-κB signaling pathway, thereby reducing liver injury via inducing gut microbiota disturbance.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33413501", "kind": "science-record", "revision": 7, "content_hash": "sha256:a7066004f37e1c0bb5bac5a1aab60129c46308352ecd9fde3b533809236ec8be", "created_at": "2026-11-01T15:41:22Z", "updated_at": "2026-11-01T22:02:54Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Alcoholic fatty liver disease inhibited the co-expression of Fmo5 and PPARα to activate the NF-κB signaling pathway, thereby reducing liver injury via inducing gut microbiota disturbance.", "doi": "10.1186/s13046-020-01782-w", "pmid": "33413501", "authors": ["Lingjian Kong", "Jing Chen", "Xiaoli Ji", "Qian Qin", "Huiyu Yang", "Dan Liu", "Deliang Li", "Meiling Sun"], "journal": "Journal of experimental & clinical cancer research : CR", "year": 2021, "abstract": "BACKGROUND: Alcohol-induced intestinal dysbiosis disrupts and inflammatory responses are essential in the development of alcoholic fatty liver disease (AFLD). Here, we investigated the effects of Fmo5 on changes in enteric microbiome composition in a model of AFLD and dissected the pathogenic role of Fmo5 in AFLD-induced liver pathology.\nMETHODS: The expression profile data of GSE8006 and GSE40334 datasets were downloaded from the GEO database. The WGCNA approach allowed us to investigate the AFLD-correlated module. DEGs were used to perform KEGG pathway enrichment analyses. Four PPI networks were constructed using the STRING database and visualized using Cytoscape software. The Cytohubba plug-in was used to identify the hub genes. Western blot and immunohistochemistry assays were used to detect protein expression. ELISA assay was used to detect the levels of serum inflammatory cytokines. Lipid droplets in the cytoplasm were observed using Oil Red O staining. Apoptosis was detected using a TUNEL assay and flow cytometry analysis. ROS levels were detected using flow cytometry analysis. Nuclear translocation of NF-κB p65 was observed using immunofluorescence staining. Co-immunoprecipitation was used to detect the co-expression of PPARα and Fmo5 in L02 cells. 16S rDNA sequencing defined the bacterial communities in mice with AFLD.\nRESULTS: Fmo5 is a key DEG and is closely associated with the gut microbiota and PPAR signaling pathway. Gut microbiome function in AFLD was significantly related to the PPAR signaling pathway. AFLD induced shifts in various bacterial phyla in the cecum, including a reduction in Bacteroidetes and increased Firmicutes. Fmo5 and PPARα co-expression in cell and animal models with AFLD, which decreased significantly. Silencing of Fmo5 and PPARα aggravated the functions of AFLD inducing apoptosis and inflammatory response, promoting liver injury, and activating the NF-κB signaling pathway in vivo and in vitro. The NF-κB inhibitor abolished the functions of silencing of Fmo5 and PPARα promoting AFLD-induced apoptosis, inflammatory response, and liver injury.\nCONCLUSION: Our data indicated that the co-expression of Fmo5 and PPARα was involved in AFLD-related gut microbiota composition and alleviated AFLD-induced liver injury, apoptosis, and inflammatory response by inhibiting the nuclear translocation of NF-κB p65 to inhibit the NF-κB signaling pathway.", "claims": [{"id": "claim-method", "statement": "In this study, DEGs in the GSE8006 dataset and GSE40334 dataset were analyzed using GEO2R. Subsequently, DEGs met the cutoff criteria of the adjusted P-value < 0.05 and |log fold change (FC)| > 1.0.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33413501", "locator": "sections[4] \"Identification of DEGs\" paragraph 2", "quote": "In this study, DEGs in the GSE8006 dataset and GSE40334 dataset were analyzed using GEO2R. Subsequently, DEGs met the cutoff criteria of the adjusted P-value < 0.05 and |log fold change (FC)| > 1.0."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated/analyzed during the current study are available.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33413501", "locator": "sections[46] \"Availability of data and materials\" paragraph 2", "quote": "The datasets generated/analyzed during the current study are available."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:33413501"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE40334"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE40334"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33413501", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s13046-020-01782-w", "sha256": "sha256:a98c2710ec8031413ffbd92f0245646b51ee71a590da554cfd1d71a9aeed3d40", "bytes": 69181, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s13046-020-01782-w", "version": null, "note": "Full article fetched from PMC; 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CO", "on and alleviated AFLD-induced liver injury, apoptosis, and inflammatory response by inhibiting the"], "order_basis": "paper_text_order:1117", "id": "assay:4"}, {"role": "data_generation", "definition_id": "flow_cytometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["optosis was detected using a TUNEL assay and flow cytometry analysis. ROS levels were detected using flo", "try analysis. ROS levels were detected using flow cytometry analysis. Nuclear translocation of NF-κB p65"], "order_basis": "paper_text_order:1164", "id": "assay:5"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": [", and activating the NF-κB signaling pathway in vivo and in vitro. The NF-κB inhibitor abolished", "sequencing defined the bacterial communities in mice with AFLD. RESULTS: Fmo5 is a key DEG and is", "mittee of the Zhengzhou University. The AFLD mouse model was established using a modified Lieber–DeCa", "fied Lieber–DeCarli liquid diet (21). 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