Eugenol inhibits preadipocyte differentiation and lipid accumulation via upregulating ATF3.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41059793", "kind": "science-record", "revision": 4, "content_hash": "sha256:bda956672e0dd5deeec75e1c51be77703f18bf5274fee84b3f5674df5dda9f53", "created_at": "2026-11-01T20:31:07Z", "updated_at": "2026-11-01T22:57:16Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Eugenol inhibits preadipocyte differentiation and lipid accumulation via upregulating ATF3.", "doi": "10.1590/1414-431X2025e14575", "pmid": "41059793", "authors": ["Pei-Pei Gu", "Lin Xu", "Patiguli Kadierjiang", "Xin Shen", "Jun Liu", "Yang Li", "Lu Zeng", "Hong-Mei Lai", "Haoshaqiang Zhang", "Jing Tao"], "journal": "Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica", "year": 2025, "abstract": "The global prevalence of overweight status and obesity has increased considerably. Obesity is the common pathological basis of numerous diseases and a crucial triggering factor for diabetes. This study aimed to investigate the role of activating transcription factor 3 (ATF3) in the adipogenic process of adipocytes and the related compounds of Chinese medicine potentially targeting ATF3. The differentially expressed genes (DEGs) in high-fat diet (HFD) or overweight patients were identified by analyzing Gene Expression Omnibus (GEO) data profiles GSE112999, GSE112740, and GSE48964. qRT-PCR and western blot were conducted to detect the expression levels of related genes. Oil-red O staining was conducted to detect lipid droplet formation within 3T3-L1 adipocytes. Compounds that interacted with ATF3 were screened through the pharmacological database and analysis platform of the traditional Chinese medicine system. Furthermore, the eugenol effect on ATF3 expression was evaluated. ATF3 expression was increased in the adipose tissues of HFD mice and in clinically obese patients. Knock down of ATF3 promoted adipocyte lipid droplet formation, upregulated the protein levels of adipocyte markers (Fabp4 and PPARγ), elevated intracellular triglyceride (TG) levels, and activated the AKT signaling pathway. Eugenol effectively promoted ATF3 expression and inhibited adipocyte differentiation and adipogenesis. ATF3 expression was found to be elevated within the adipose tissues of overweight patients, whereas ATF3 knockdown promoted adipocyte differentiation and lipid accumulation by activating the PI3K/AKT signaling pathway. Therefore, ATF3 overexpression or supplementation with eugenol may be a potential method for overcoming obesity.", "claims": [{"id": "claim-method", "statement": "The R language limma package was used to perform differential gene analysis on these datasets, with the screening standard as |logFC |>1 and corrected by P<0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41059793", "locator": "sections[3] \"GEO data analysis\" paragraph 2", "quote": "The R language limma package was used to perform differential gene analysis on these datasets, with the screening standard as |logFC |>1 and corrected by P<0.05."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Datasets GSE112999, GSE112740, and GSE48964 were downloaded from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). The GSE112999 dataset was analyzed on white adipose tissues of 6-10 week-old male C57BL/6J mice, including 9 cases with a low-fat diet (LFD) and 9 cases with a high-fat diet (HFD).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41059793", "locator": "sections[3] \"GEO data analysis\" paragraph 2", "quote": "Datasets GSE112999, GSE112740, and GSE48964 were downloaded from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). The GSE112999 dataset was analyzed on white adipose tissues of 6-10 week-old male C57BL/6J mice, including 9 cases with a low-fat diet (LFD) and 9 cases with a high-fat diet (HFD)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "", "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:41059793"], "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:GSE112740"], "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": {"fold_change": "reening by absolute log fold change and corrected P value"}, "inputs": ["data:geo:GSE112740"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:41059793", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1590/1414-431X2025e14575", "sha256": "sha256:423c08b2494364121faedc3ecd76834b22aa15a0929534d8db9fb93d72e72f48", "bytes": 26148, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1590/1414-431X2025e14575", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12513698", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE112740", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE112740", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE112740", "version": null, "note": "Datasets GSE112999, GSE112740, and GSE48964 were downloaded from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). The GSE112999 dataset was analyzed on white adipose tissues of 6-10 week-old male C57BL/6J mice, including 9 cases with a low-fat diet (LFD) and 9 cases with a high-fat diet (HFD).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Datasets GSE112999, GSE112740, and GSE48964 were downloaded from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). The GSE112999 dataset was analyzed on white adipose tissues of 6-10 week-old male C57BL/6J mice, including 9 cases with a low-fat diet (LFD) and 9 cases with a high-fat diet (HFD).", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM3082780", "GSM3082781", "GSM3082782", "GSM3082783", "GSM3082784", "GSM3082785"], "sample_count": 6, "group_sizes": null, "group_sizes_basis": null, "platform": "19057", "taxon": "Mus musculus", "title": "RNA sequencing of brown adipose tissue of lean and obese mice", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE112999", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE112999", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE112999", "version": null, "note": "Datasets GSE112999, GSE112740, and GSE48964 were downloaded from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). The GSE112999 dataset was analyzed on white adipose tissues of 6-10 week-old male C57BL/6J mice, including 9 cases with a low-fat diet (LFD) and 9 cases with a high-fat diet (HFD).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Datasets GSE112999, GSE112740, and GSE48964 were downloaded from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). The GSE112999 dataset was analyzed on white adipose tissues of 6-10 week-old male C57BL/6J mice, including 9 cases with a low-fat diet (LFD) and 9 cases with a high-fat diet (HFD).", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM3093043", "GSM3093044", "GSM3093045", "GSM3093046", "GSM3093047", "GSM3093048", "GSM3093049", "GSM3093050", "GSM3093051", "GSM3093052", "GSM3093053", "GSM3093054", "GSM3093055", "GSM3093056", "GSM3093057", "GSM3093058", "GSM3093059", "GSM3093060"], "sample_count": 18, "group_sizes": null, "group_sizes_basis": null, "platform": "19057", "taxon": "Mus musculus", "title": "RNA sequencing of white adipose tissue of lean and obese mice", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE48964", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE48964", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE48964", "version": null, "note": "Datasets GSE112999, GSE112740, and GSE48964 were downloaded from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). The GSE112999 dataset was analyzed on white adipose tissues of 6-10 week-old male C57BL/6J mice, including 9 cases with a low-fat diet (LFD) and 9 cases with a high-fat diet (HFD).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Datasets GSE112999, GSE112740, and GSE48964 were downloaded from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). The GSE112999 dataset was analyzed on white adipose tissues of 6-10 week-old male C57BL/6J mice, including 9 cases with a low-fat diet (LFD) and 9 cases with a high-fat diet (HFD).", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM1187673", "GSM1187674", "GSM1187675", "GSM1187676", "GSM1187677", "GSM1187678"], "sample_count": 6, "group_sizes": null, "group_sizes_basis": null, "platform": "6244", "taxon": "Homo sapiens", "title": "Expression data from Adipose Stem Cells (ASC) from morbidly obese and non-obese individuals", "resolution_checked_at": "2026-11-01T18:46:34Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE112740 not downloaded", "asset:data:geo:GSE112740 licence not read", "asset:data:geo:GSE112999 not downloaded", "asset:data:geo:GSE112999 licence not read", "asset:data:geo:GSE48964 not downloaded", "asset:data:geo:GSE48964 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {"fold_change": "reening by absolute log fold change and corrected P value"}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The R language limma package was used to perform differential gene analysis on these datasets, with the screening standard as |logFC |>1 and corrected by P<0.05."}}, {"id": "method-2", "family": "group_comparison", "specific": "student_t_test", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["student_t"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Student's t-test"}}, {"id": "method-3", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "ANOVA"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE112999", "GSE112740", "GSE48964"], "resolved_accessions": ["GSE112999", "GSE112740", "GSE48964"], "statements": ["Datasets GSE112999, GSE112740, and GSE48964 were downloaded from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). The GSE112999 dataset was analyzed on white adipose tissues of 6-10 week-old male C57BL/6J mice, including 9 cases with a low-fat diet (LFD) and 9 cases with a high-fat diet (HFD)."], "basis": "The paper names GSE112999, GSE112740, GSE48964 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:41059793", "data:geo:GSE112740"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE112740"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T20:02:48Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 5, "usage": {"prompt_tokens": 7867, "completion_tokens": 1132, "cached_tokens": 128}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:41059793", "type": "paper", "label": "pmid:41059793"}, {"id": "source:pmid:41059793", "type": "manuscript", "label": "PMID 41059793 full text"}, {"id": "data:geo:GSE112740", "type": "dataset", "label": "GEO GSE112740"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:41059793", "type": "paper", "label": "pmid:41059793"}, {"id": "source:pmid:41059793", "type": "manuscript", "label": "PMID 41059793 full text"}, {"id": "data:geo:GSE112740", "type": "dataset", "label": "GEO GSE112740"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-41059793", "type": "extraction", "used": ["source:pmid:41059793"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE112740", "type": "accession_resolution", "used": ["data:geo:GSE112740"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:41059793", "parent_hash": "sha256:8dbb5f8a672f2bc236501a69a34a2bdeb68c870d5661d66590e48e8aee37c635", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE112740 licence not read", "asset:data:geo:GSE112740 not downloaded", "asset:data:geo:GSE112999 licence not read", "asset:data:geo:GSE112999 not downloaded", "asset:data:geo:GSE48964 licence not read", "asset:data:geo:GSE48964 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["112999, GSE112740, and GSE48964. qRT-PCR and western blot were conducted to detect the expression leve"], "order_basis": "paper_text_order:646", "id": "assay:1"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ted to detect lipid droplet formation within 3T3-L1 adipocytes. Compounds that interacted with A", "ake a single-cell suspension, which was then passaged at a 1:2-1:3 ratio. The cells were cultured", "Methods Cell culture The mouse preadipocyte 3T3-L1 (#GNM25) cell line was procured from the Cel", "of the Chinese Academy of Sciences (China). 3T3-L1 cells were cultivated in DMEM high glucose m"], "order_basis": "paper_text_order:798", "id": "assay:2"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["tissues of overweight patients, whereas ATF3 knockdown promoted adipocyte differentiation and lipid"], "order_basis": "paper_text_order:1567", "id": "assay:3"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["Material and Methods Cell culture The mouse preadipocyte 3T3-L1 (#GNM25) cell line was p"], "order_basis": "paper_text_order:1839", "id": "assay:4"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The R language limma package was used to perform differential gene analysis on these datasets, with the screening standard as |logFC |>1 and corrected by P<0.05."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}