title: Eicosapentaenoic acid inhibits intestinal β-carotene absorption by downregulation of lipid transporter expression via PPAR-α dependent mechanism.
abstract: The involvement of lipid transporters, the scavenger receptor class B, type I (SR-BI) and Niemann-Pick type C1 Like 1 protein (NPC1L1) in carotenoid absorption is demonstrated in intestinal cells and animal models. Dietary ω-3 fatty acids are known to possess antilipidemic properties, which could be mediated by activation of PPAR family transcription factors. The present study was conducted to determine the effect of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), on intestinal β-carotene absorption. β-carotene uptake in Caco-2/TC7 cells was inhibited by EPA (p < 0.01) and PPARα agonist (P < 0.01), but not by DHA, PPARγ or PPARδ agonists. Despite unaltered β-carotene uptake, both DHA and PPARδ agonists inhibited the NPC1L1 expression. Further, EPA also induced the expression of carnitine palmitoyl transferase 1A (CPT1A) expression, a PPARα target gene. Interestingly, EPA induced inhibition of β-carotene uptake and SR B1 expression were abrogated by specific PPARα antagonist, but not by PPARδ antagonist. EPA and PPARα agonist also inhibited the basolateral secretion of β-carotene from Caco-2 cells grown on permeable supports. These results suggest that EPA inhibits intestinal β-carotene absorption by down regulation of SR B1 expression via PPARα dependent mechanism and provide an evidence for dietary modulation of intestinal β-carotene absorption.
authors.affiliation: Biophysics Division, National Institute of Nutrition, Jamai Osmania, Hyderabad 500007, India.
authors.forename: Purna Chandra
authors.initials: PC
authors.lastname: Mashurabad
authors.affiliation: Biophysics Division, National Institute of Nutrition, Jamai Osmania, Hyderabad 500007, India.
authors.forename: Palsa
authors.initials: P
authors.lastname: Kondaiah
authors.affiliation: Biophysics Division, National Institute of Nutrition, Jamai Osmania, Hyderabad 500007, India.
authors.forename: Ravindranadh
authors.initials: R
authors.lastname: Palika
authors.affiliation: Biophysics Division, National Institute of Nutrition, Jamai Osmania, Hyderabad 500007, India.
authors.forename: Sudip
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Biophysics Division, National Institute of Nutrition, Jamai Osmania, Hyderabad 500007, India.
authors.forename: Madhavan K
authors.initials: MK
authors.lastname: Nair
authors.affiliation: Biophysics Division, National Institute of Nutrition, Jamai Osmania, Hyderabad 500007, India. Electronic address: raghu_nin2000@yahoo.com.
authors.forename: Pullakhandam
authors.initials: P
authors.lastname: Raghu
mesh_terms: D018938:Caco-2 Cells; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage*; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology; D047493:PPAR alpha / Q000378:metabolism*; D051122:Scavenger Receptors, Class B / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D019207:beta Carotene / Q000378:metabolism*
chemical_list: D047493:PPAR alpha; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D019207:beta Carotene; D015118:Eicosapentaenoic Acid
keywords: Caco-2 cells; DHA; EPA; NPC1L1; PPARs; SR B1; β-Carotene