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Papers In Press, published online ahead of print July 16, 2005
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Endocrinology, Leiden University Medical Centre, Leiden 2333 ZA
Corresponding Author: a.m.den_boer{at}lumc.nl
CD36 is involved in high affinity peripheral FFA uptake. Mice lacking CD36 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-deficient (cd36 -/-) mice. Cd36 -/- mice showed no differences in hepatic VLDL-TG production or intestinal [3H]TG uptake as compared to wild-type littermates. Importantly, the postprandial TG response upon an intragastric fat load was enhanced 2-fold in cd36 -/- mice compared to wild-type mice (13 ± 6 vs 7 ± 2 mM.h; P<0.05), with a concomitant 2.5-fold increased FFA response (20 ± 6 vs 8 ± 1 mM.h; P<0.05), suggesting that the elevated FFA in cd36 -/- mice may impair LPL-mediated TG hydrolysis. Postheparin plasma lipoprotein lipase (LPL) levels were not different between cd36 -/- and wild-type mice. However, the in vitro LPL-mediated TG-hydrolysis rate as induced by post-heparin plasma of cd36 -/- mice in absence of excess FFA-free BSA was reduced by 51% compared to wild-type littermates (0.13 ± 0.06 vs 0.27 ± 0.07 nmol oleate/mL/min P < 0.05). This inhibition was relieved upon addition of excess FFA-free BSA. To study whether LPL activity can be decreased in vivo via product inhibition by FFA, we increased plasma FFA in wild-type mice by infusion and showed that the plasma half-life of glycerol tri[3H]oleate-labeled VLDL-like emulsion particles was increased 2.5-fold (t½ = 17.5 ± 10.4 vs 7.0 ± 2.6 min, P<0.05) as compared to vehicle-infused mice. We conclude that the increased plasma TG levels observed in cd36 -/- mice do not result from an increased hepatic VLDL-TG production or intestinal lipid absorption, but are caused by decreased LPL-mediated hydrolysis of TG-rich lipoproteins resulting from FFA-induced product inhibition of LPL.
Accepted on July 15, 2005
CD36 deficiency in mice impairs lipoprotein lipase-mediated triglyceride clearance
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