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Micellar lipid composition profoundly affects LXR-dependent cholesterol transport across CaCo2 cells |
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| Authors: | Michele Petruzzelli Albert K Groen Karel J van Erpecum Carlos Vrins Astrid E van der Velde Giuseppe Palasciano Giuseppe Lo Sasso Antonio Moschetta |
| Institution: | a Department of Experimental Hepatology, Academic Medical Center, Amsterdam, The Netherlands b Department of Medical Biochemistry, Academic Medical Center, Amsterdam, The Netherlands c Department of Gastroenterology and Hepatology, University Hospital Utrecht, The Netherlands d Clinica Medica “A. Murri”, Department of Internal and Public Medicine, University of Bari, Italy e Laboratory of Lipid Metabolism and Cancer, Consorzio Mario Negri Sud, Via Nazionale 8/A, 66030 Santa Maria Imbaro (Chieti), Italy |
| Abstract: | Intraluminal phospholipids affect micellar solubilization and absorption of cholesterol. We here study cholesterol transport from taurocholate-phospholipid-cholesterol micelles to CaCo2 cells, and associated effects on ABC-A1 mediated cholesterol efflux. Micellar incorporation of egg-yolk-phosphatidylcholine markedly increased apical retention of the sterol with decreased expression of ABC-A1, an effect that is prevented by synthetic liver X receptor (LXR) or retinoid X receptor (RXR) agonists. On the other hand, incorporation of lyso-phosphatidylcholine (LysoPC) increased ABC-A1-HDL-dependent basolateral cholesterol efflux, an effect that is abated when LXR is silenced. Thus, the modulation of cholesterol metabolism via intraluminal phospholipids is related to the activity of the oxysterol nuclear receptor LXR. |
| Keywords: | ABC ATP-binding casette DMEM Dulbecco&rsquo s minimum essential medium FCS fetal calf serum HDL high density lipoprotein LysoPC Lyso-phosphatidylcholine LXR liver X receptor NPC1L1 Niemann-Pick C1-like-1 PC Phosphatidylcholine RXR retinoid X receptor SM sphingomyelin TC taurocholate |
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