title: Chylomicron- and VLDL-derived lipids enter the heart through different pathways: in vivo evidence for receptor- and non-receptor-mediated fatty acid uptake.
abstract: Lipids circulate in the blood in association with plasma lipoproteins and enter the tissues either after hydrolysis or as non-hydrolyzable lipid esters. We studied cardiac lipids, lipoprotein lipid uptake, and gene expression in heart-specific lipoprotein lipase (LpL) knock-out (hLpL0), CD36 knock-out (Cd36(-/-)), and double knock-out (hLpL0/Cd36(-/-)-DKO) mice. Loss of either LpL or CD36 led to a significant reduction in heart total fatty acyl-CoA (control, 99.5 ± 3.8; hLpL0, 36.2 ± 3.5; Cd36(-/-), 57.7 ± 5.5 nmol/g, p < 0.05) and an additive effect was observed in the DKO (20.2 ± 1.4 nmol/g, p < 0.05). Myocardial VLDL-triglyceride (TG) uptake was reduced in the hLpL0 (31 ± 6%) and Cd36(-/-) (47 ± 4%) mice with an additive reduction in the DKO (64 ± 5%) compared with control. However, LpL but not CD36 deficiency decreased VLDL-cholesteryl ester uptake. Endogenously labeled mouse chylomicrons were produced by tamoxifen treatment of β-actin-MerCreMer/LpL(flox/flox) mice. Induced loss of LpL increased TG levels >10-fold and reduced HDL by >50%. After injection of these labeled chylomicrons in the different mice, chylomicron TG uptake was reduced by ∼70% and retinyl ester by ∼50% in hLpL0 hearts. Loss of CD36 did not alter either chylomicron TG or retinyl ester uptake. LpL loss did not affect uptake of remnant lipoproteins from ApoE knock-out mice. Our data are consistent with two pathways for fatty acid uptake; a CD36 process for VLDL-derived fatty acid and a non-CD36 process for chylomicron-derived fatty acid uptake. In addition, our data show that lipolysis is involved in uptake of core lipids from TG-rich lipoproteins.
authors.affiliation: Division of Preventive Medicine and Nutrition, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
authors.forename: Kalyani G
authors.initials: KG
authors.lastname: Bharadwaj
authors.forename: Yaeko
authors.initials: Y
authors.lastname: Hiyama
authors.forename: Yunying
authors.initials: Y
authors.lastname: Hu
authors.forename: Lesley Ann
authors.initials: LA
authors.lastname: Huggins
authors.forename: Rajasekhar
authors.initials: R
authors.lastname: Ramakrishnan
authors.forename: Nada A
authors.initials: NA
authors.lastname: Abumrad
authors.forename: Gerald I
authors.initials: GI
authors.lastname: Shulman
authors.forename: William S
authors.initials: WS
authors.lastname: Blaner
authors.forename: Ira J
authors.initials: IJ
authors.lastname: Goldberg
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000493:pharmacokinetics; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D015243:Cholesterol, VLDL / Q000235:genetics / Q000378:metabolism*; D002914:Chylomicrons / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000235:genetics / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology*; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology; D014280:Triglycerides / Q000235:genetics / Q000378:metabolism*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D018955:CD36 Antigens; D015243:Cholesterol, VLDL; D002914:Chylomicrons; D005227:Fatty Acids; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride; D013629:Tamoxifen; D008071:Lipoprotein Lipase