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: Regulation of sterol regulatory element-binding proteins (SREBPs) by fatty acid flux was investigated in CaCo-2 cells. Cells were incubated with 1 mM taurocholate with or without 250 microM 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.
authors.affiliation: Department of Veterans Affairs, Iowa City, IA 52242, USA. f-jeffrey-field@uiowa.edu
authors.forename: F Jeffrey
authors.initials: FJ
authors.lastname: Field
authors.forename: Ella
authors.initials: E
authors.lastname: Born
authors.forename: Shubha
authors.initials: S
authors.lastname: Murthy
authors.forename: Satya N
authors.initials: SN
authors.lastname: Mathur
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000924:Anticholesteremic Agents / Q000494:pharmacology; D001055:Apolipoproteins B / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins / Q000096:biosynthesis*; D018938:Caco-2 Cells; D002784:Cholesterol / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D064429:Fatty Acid Synthases / Q000096:biosynthesis*; D005227:Fatty Acids / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D006845:Hydrocarbons, Fluorinated; D015151:Immunoblotting; D010957:Plasmids / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012260:Ribonucleases / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1; D013449:Sulfonamides; D014157:Transcription Factors; D014280:Triglycerides / Q000378:metabolism*; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D000103:Acetyl-CoA Carboxylase; D000924:Anticholesteremic Agents; D001055:Apolipoproteins B; D022762:CCAAT-Enhancer-Binding Proteins; D002784:Cholesterol; D004268:DNA-Binding Proteins; D015118:Eicosapentaenoic Acid; D064429:Fatty Acid Synthases; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D006845:Hydrocarbons, Fluorinated; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D012260:Ribonucleases; D051780:Sterol Regulatory Element Binding Protein 1; D013449:Sulfonamides; D014157:Transcription Factors; D014280:Triglycerides; C497387:SREBF1 protein, human; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides