A null mutation in murine CD36 reveals an important role in fatty acid and lipoprotein metabolism.
A null mutation in the scavenger receptor gene CD36 was created in mice by targeted homologous recombination. These mice produced no detectable CD36 protein, were viable, and bred normally. A significant decrease in binding and uptake of oxidized low density lipoprotein was observed in peritoneal macrophages of null mice as compared with those from control mice. CD36 null animals had a significant increase in fasting levels of cholesterol, nonesterified free fatty acids, and triacylglycerol. The increase in cholesterol was mainly within the high density lipoprotein fraction, while the increase in triacylglycerol was within the very low density lipoprotein fraction. Null animals had lower fasting serum glucose levels when compared with wild type controls. Uptake of 3H-labeled oleate was significantly reduced in adipocytes from null mice. However, the decrease was limited to the low ratios of fatty acid:bovine serum albumin, suggesting that CD36 was necessary for the high affinity component of the uptake process. The data provide evidence for a functional role for CD36 in lipoprotein/fatty acid metabolism that was previously underappreciated.
Febbraio
M
M
Division of Hematology/Oncology, Department of Medicine, Weill Medical College of Cornell University, New York, New York 10021, USA. mjfebbra@mail.med.cornell.edu
Abumrad
N A
NA
Hajjar
D P
DP
Sharma
K
K
Cheng
W
W
Pearce
S F
SF
Silverstein
R L
RL
D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D018955:CD36 Antigens / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D005227:Fatty Acids / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D018955:CD36 Antigens; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D008077:Lipoproteins, LDL; D014280:Triglycerides; C099252:oxidized low density lipoprotein; D002784:Cholesterol