CD36 deficiency in mice impairs lipoprotein lipase-mediated triglyceride clearance
article
CD36 is involved in high-affinity peripheral FFA uptake. CD36-deficient (cd36-/-) mice exhibit increased plasma FFA and triglyceride (TG) levels. The aim of the present study was to elucidate the cause of the increased plasma TG levels in cd36-/- mice. cd36-/- mice showed no differences in hepatic VLDL-TG production or intestinal [3H]TG uptake compared with wild-type littermates. cd36-/- mice showed a 2-fold enhanced postprandial TG response upon an intragastric fat load (P < 0.05), with a concomitant 2.5-fold increased FFA response (P < 0.05), suggesting that the increased FFA in cd36-/- mice may impair LPL-mediated TG hydrolysis. Postheparin LPL levels were not affected. However, the in vitro LPL-mediated TG hydrolysis rate as induced by postheparin plasma of cd36 -/- mice in the absence of excess FFA-free BSA was reduced 2-fold compared with wild-type plasma (P < 0.05). This inhibition was relieved upon the addition of excess FFA-free BSA. Likewise, increasing plasma FFA in wild-type mice to the levels observed hi cd36-/- mice by infusion prolonged the plasma half-life of glycerol tri[3H]oleate-labeled VLDL-like emulsion particles by 2.5-fold (P < 0.05). We conclude that the increased plasma TG levels observed in cd36-/- mice are caused by decreased LPL-mediated hydrolysis of TG-rich lipoproteine resulting from FFA-induced product inhibition of LPL. Copyright © 2005 by the American Society for Biochemistry and Molecular Biology, Inc. Chemicals / CAS: glycerol, 56-81-5; heparin, 37187-54-5, 8057-48-5, 8065-01-8, 9005-48-5; lipoprotein lipase, 83137-80-8, 9004-02-8; Antigens, CD36; Fatty Acids, Nonesterified; Lipoprotein Lipase, EC 3.1.1.34; Lipoproteins, VLDL; Triglycerides; very low density lipoprotein triglyceride
Topics
Biomedical ResearchFatty acid transportFree fatty acidsPostprandial lipid metabolismTransgenic miceTriglyceride hydrolysisCD36 antigenGlycerolHeparinTriacylglycerolVery low density lipoproteinAnimal experimentAnimal tissueBody fatCD36 deficiencyControlled studyEnzyme inhibitionEnzyme metabolismHalf life timeIn vitro studyIsotope labelingLipid metabolismMouseNonhumanProtein deficiencyProtein functionProtein hydrolysisTransgenic mouseTiacylglycerol blood levelWild typeAnimalsAntigens, CD36EatingFatty Acids, NonesterifiedFemaleIntestinal AbsorptionLipoprotein LipaseLipoproteins, VLDLLiverMaleMiceMice, Inbred C57BLTriglycerides
TNO Identifier
238739
ISSN
00222275
Source
Journal of Lipid Research, 46(10), pp. 2175-2181.
Pages
2175-2181