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PubMed · 12213084

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.

F Jeffrey Field·Ella Born·Shubha Murthy·Satya N Mathur
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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.

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Acetyl-CoA CarboxylaseAnticholesteremic AgentsApolipoproteins BCCAAT-Enhancer-Binding ProteinsCaco-2 CellsCholesterolDNA-Binding ProteinsDose-Response Relationship, DrugEicosapentaenoic AcidFatty Acid SynthasesFatty AcidsFatty Acids, UnsaturatedGene ExpressionHumansHydrocarbons, FluorinatedImmunoblottingPlasmidsRNA, MessengerReceptors, Cytoplasmic and NuclearReverse Transcriptase Polymerase Chain ReactionRibonucleasesSterol Regulatory Element Binding Protein 1SulfonamidesTranscription FactorsTriglyceridesFluorocarbonsBenzenesulfonamidesJournal ArticleResearch Support, U.S. Gov't, Non-P.H.S.Research Support, U.S. Gov't, P.H.S.

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F Jeffrey Field, Ella Born, Shubha Murthy, Satya N Mathur. 2002-12-15. 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.. https://doi.org/10.1042/bj20020731

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