CD36 deficiency in mice impairs lipoprotein lipase-mediated triglyceride clearance.
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 [(3)H]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 in cd36(-)(/)(-) mice by infusion prolonged the plasma half-life of glycerol tri[(3)H]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 lipoproteins resulting from FFA-induced product inhibition of LPL.
Goudriaan
Jeltje R
JR
Netherlands Organization for Applied Scientific Research-Quality of Life, Gaubius Laboratory, Leiden, The Netherlands.
den Boer
Marion A M
MA
Rensen
Patrick C N
PC
Febbraio
Maria
M
Kuipers
Folkert
F
Romijn
Johannes A
JA
Havekes
Louis M
LM
Voshol
Peter J
PJ
D000818:Animals; D018955:CD36 Antigens / Q000235:genetics*; D004435:Eating; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D007408:Intestinal Absorption / Q000502:physiology; D008071:Lipoprotein Lipase / Q000097:blood / Q000502:physiology*; D008079:Lipoproteins, VLDL / Q000096:biosynthesis; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014280:Triglycerides / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*
D018955:CD36 Antigens; D005230:Fatty Acids, Nonesterified; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride; D008071:Lipoprotein Lipase