{"doi":"10.1042/bj20020731","title":"Polyunsaturated fatty acids decrease the expression of sterol regulatory element-binding protein-1 in CaCo-2 cells: effect on fatty acid synthesis and triacylglycerol transport","abstract":"<jats:p>Regulation of sterol regulatory element-binding proteins (SREBPs) by fatty acid flux was investigated in CaCo-2 cells. Cells were incubated with 1mM taurocholate with or without 250μM 18:0, 18:1, 18:2, 20:4, 20:5 or 22:6 fatty acids. Fatty acid synthase (FAS) and acetyl-CoA carboxylase mRNA levels and gene and protein expression of SREBPs were estimated. 18:2, 20:4, 20:5 and 22:6 fatty acids decreased the amount of mature SREBP-1 and mRNA levels of SREBP-1c, SREBP-1a, FAS and acetyl-CoA carboxylase. SREBP-2 gene or mature protein expression was not altered. Liver X receptor (LXR) activation by T0901317 increased gene expression of SREBP-1c, SREBP-1a, FAS and acetyl-CoA carboxylase without altering SREBP-2. 20:5, but not 18:1, prevented the full expression of SREBP-1c mRNA by T0901317. T0901317 increased SREBP-1 mass without altering the mass of mature SREBP-2. Although only 18:2, 20:4, 20:5 and 22:6 suppressed SREBP-1, acetyl-CoA carboxylase and FAS expression, all fatty acids decreased the rate of fatty acid synthesis. T0901317 increased endogenous fatty acid synthesis yet did not increase secretion of triacylglycerol-rich lipoproteins. In CaCo-2 cells, polyunsaturated fatty acids decrease gene and protein expression of SREBP-1 and FAS mRNA, probably through interference with LXR activity. Since all fatty acids decreased fatty acid synthesis, mechanisms other than changes in SREBP-1c expression must be entertained. Increased endogenous fatty acid synthesis does not promote triacylglycerol-rich lipoprotein secretion.</jats:p>","journal":"Biochemical Journal","year":2002,"id":622814,"datarank":0.6414999178524083,"base_score":4.276666119016055,"endowment":4.276666119016055,"self_citation_contribution":0.6414999178524083,"citation_network_contribution":0.0,"self_endowment_contribution":0.6414999178524083,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":71,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1609397,"name":"Ella BORN","orcid":null,"position":1,"is_corresponding":false},{"id":1609398,"name":"Shubha MURTHY","orcid":null,"position":2,"is_corresponding":false},{"id":1609399,"name":"Satya N. MATHUR","orcid":null,"position":3,"is_corresponding":false},{"id":1609396,"name":"F. Jeffrey FIELD","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Polyunsaturated fatty acids decrease the expression of sterol regulatory element-binding protein-1 in CaCo-2 cells: effect on fatty acid synthesis and triacylglycerol transport","abstract":"<jats:p>Regulation of sterol regulatory element-binding proteins (SREBPs) by fatty acid flux was investigated in CaCo-2 cells. Cells were incubated with 1mM taurocholate with or without 250μM 18:0, 18:1, 18:2, 20:4, 20:5 or 22:6 fatty acids. Fatty acid synthase (FAS) and acetyl-CoA carboxylase mRNA levels and gene and protein expression of SREBPs were estimated. 18:2, 20:4, 20:5 and 22:6 fatty acids decreased the amount of mature SREBP-1 and mRNA levels of SREBP-1c, SREBP-1a, FAS and acetyl-CoA carboxylase. SREBP-2 gene or mature protein expression was not altered. Liver X receptor (LXR) activation by T0901317 increased gene expression of SREBP-1c, SREBP-1a, FAS and acetyl-CoA carboxylase without altering SREBP-2. 20:5, but not 18:1, prevented the full expression of SREBP-1c mRNA by T0901317. T0901317 increased SREBP-1 mass without altering the mass of mature SREBP-2. Although only 18:2, 20:4, 20:5 and 22:6 suppressed SREBP-1, acetyl-CoA carboxylase and FAS expression, all fatty acids decreased the rate of fatty acid synthesis. T0901317 increased endogenous fatty acid synthesis yet did not increase secretion of triacylglycerol-rich lipoproteins. In CaCo-2 cells, polyunsaturated fatty acids decrease gene and protein expression of SREBP-1 and FAS mRNA, probably through interference with LXR activity. Since all fatty acids decreased fatty acid synthesis, mechanisms other than changes in SREBP-1c expression must be entertained. Increased endogenous fatty acid synthesis does not promote triacylglycerol-rich lipoprotein secretion.</jats:p>","is_dataset_classified":null,"base_score":4.276666119016055,"endowment":4.276666119016055,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"12213084","pmcid":"PMC1223029","openalex_id":"https://openalex.org/W1994623425","authors":[],"funders":[{"funder_name":"NHLBI NIH HHS","grant_id":"HL49264","title":null}],"total_grants":1,"fwci":4.2369,"citation_percentile":0.94127294,"influential_citations":0,"citation_trend":[{"year":2012,"count":1},{"year":2013,"count":4},{"year":2014,"count":2},{"year":2015,"count":3},{"year":2016,"count":1},{"year":2017,"count":3},{"year":2018,"count":2},{"year":2024,"count":2},{"year":2025,"count":1},{"year":2026,"count":1}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1223029","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1223029","host_type":"repository"},{"url":"https://portlandpress.com/biochemj/article-pdf/368/3/855/710036/bj3680855.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1042/bj20020731","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/12213084","host_type":"repository"}],"fields_of_study":["Cholesterol and Lipid Metabolism","Peroxisome Proliferator-Activated Receptors","Drug Transport and Resistance Mechanisms"],"mesh_terms":["Benzenesulfonamides","Acetyl-CoA Carboxylase","Anticholesteremic Agents","Apolipoproteins B","Cholesterol","DNA-Binding Proteins","Dose-Response Relationship, Drug","Fatty Acids","Fatty Acids, Unsaturated","Fluorocarbons","Humans","Hydrocarbons, Fluorinated","Plasmids","Ribonucleases","RNA, Messenger","Sulfonamides","Transcription Factors","Triglycerides","Eicosapentaenoic Acid","Immunoblotting","Gene Expression","Receptors, Cytoplasmic and Nuclear","Caco-2 Cells","Reverse Transcriptase Polymerase Chain Reaction","CCAAT-Enhancer-Binding Proteins","Sterol Regulatory Element Binding Protein 1","Fatty Acid Synthases"],"keywords":["Sterol regulatory element-binding protein","Fatty acid synthase","Fatty acid synthesis","Acetyl-CoA carboxylase","Polyunsaturated fatty acid","Fatty acid","Biochemistry","Free fatty acid receptor","Liver X receptor","Biology","Sterol","Pyruvate carboxylase","adipocyte protein 2","Chemistry","Cholesterol","Transcription factor","Enzyme","Gene"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Clean water and sanitation"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T21:08:51.244307Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}