title: Isomer-specific effects of conjugated linoleic acid on HDL functionality associated with reverse cholesterol transport.
abstract: High-density lipoproteins (HDLs) are atheroprotective because of their role in reverse cholesterol transport. The intestine is involved in this process because it synthesizes HDL, removes cholesterol from plasma and excretes it into the lumen. We investigated the role of selected dietary fatty acids on intestinal cholesterol uptake and HDL functionality. Caco-2 monolayers grown on Transwells were supplemented with either palmitic, palmitoleic, oleic, linoleic, docosahexaenoic, eicosapentaenoic, arachidonic or conjugated linoleic acids (CLAs): c9,t11-CLA; t9,t11-CLA; c10,t12-CLA. Cells synthesized HDL in the basolateral compartment for 24 h in the absence or presence of an antibody to SR-BI (aSR-BI), which inhibits its interaction with HDL. Free cholesterol (FC) accumulated to a greater extent in the presence than in the absence of aSR-BI, indicating net uptake of FC by SR-BI. Uptake's efficiency was significantly decreased when cells were treated with c9,t11-CLA relative to the other fatty acids. These differences were associated with lower HDL functionality, since neither SR-BI protein expression nor expression and alternative splicing of other genes involved lipid metabolism were affected. Only INSIG2 expression was decreased, with no increase of its target genes. Increasing pre-β-HDL synthesis, by inducing ABCA1 and adding APOA1, resulted in reduced uptake of FC by SR-BI after c9,t11-CLA treatment, indicating reduced functionality of pre-β-HDL. Conversely, treatment with c9,t11-CLA resulted in a greater uptake of FC and esterified cholesterol from mature HDL. Therefore, Caco-2 monolayers administered c9,t11-CLA produced a nonfunctional pre-β-HDL but took up cholesterol more efficiently via SR-BI from mature HDL.
authors.affiliation: Laboratory of Functional Foods, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM + CSIC, Madrid, Spain.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Nicod
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca NY, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Parker
authors.affiliation: Laboratory of Functional Foods, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM + CSIC, Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Giordano
authors.affiliation: Laboratory of Functional Foods, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM + CSIC, Madrid, Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: Maestro
authors.affiliation: Laboratory of Functional Foods, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM + CSIC, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Davalos
authors.affiliation: Laboratory of Functional Foods, Madrid Institute for Advanced Studies (IMDEA)-Food, CEI UAM + CSIC, Madrid, Spain. Electronic address: francesco.visioli@imdea.org.
authors.forename: Francesco
authors.initials: F
authors.lastname: Visioli
mesh_terms: D017398:Alternative Splicing; D001692:Biological Transport; D018955:CD36 Antigens / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018938:Caco-2 Cells; D016764:Cell Polarity; D002788:Cholesterol Esters / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood / Q000378:metabolism*; D020895:Enterocytes / Q000166:cytology / Q000378:metabolism*; D004764:Enterohepatic Circulation; D005786:Gene Expression Regulation; D053442:High-Density Lipoproteins, Pre-beta / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007408:Intestinal Absorption; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D044243:Linoleic Acids, Conjugated / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000097:blood / Q000378:metabolism*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D018955:CD36 Antigens; D002788:Cholesterol Esters; D002791:Cholesterol, Dietary; D008076:Cholesterol, HDL; D053442:High-Density Lipoproteins, Pre-beta; C467727:INSIG2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D044243:Linoleic Acids, Conjugated; D008075:Lipoproteins, HDL; D008565:Membrane Proteins; C503589:cis-9, trans-11-conjugated linoleic acid; C496197:trans-10,cis-12-conjugated linoleic acid; C046938:9,11-linoleic acid
keywords: Atherosclerosis; Conjugated linoleic acid; HDL functionality; Intestine; SR-BI