Role of hepatic lipase and scavenger receptor BI in clearing phospholipid/free cholesterol-rich lipoproteins in PLTP-deficient mice.
Phospholipid transfer protein knock-out (PLTP0) mice have defective transfer of phospholipids (PL) from triglyceride-rich lipoproteins (TRL) into high-density lipoproteins (HDL). In this study, we examined the role of diet, hepatic lipase (HL) and scavenger receptor BI (SRBI) in determining the accumulation of excess PL and free cholesterol (FC, "surface remnants") in plasma of PLTP0 mice. PL and FC accumulated in the very low-density lipoprotein (VLDL)-LDL region of PLTP0 mice on a highly saturated, coconut oil-based diet, but not on chow or milk-fat based Western diets. Accumulation of PL and FC was dramatically increased in PLTP0/HL0 mice, compared to PLTP0 mice, but only on the coconut oil diet. Turnover studies indicated that the coconut oil diet was associated with delayed catabolism of PL of PL/FC-rich particles. Incubation of these particles with primary hepatocytes in the presence of SRBI neutralizing antibody indicated that SRBI was primarily responsible for removal of FC and PL on the Western diet. In hepatocytes of coconut oil-fed mice, removal of FC and PL from these particles by SRBI was markedly reduced, even though SRBI protein expression levels were unchanged. These studies indicate that HL and SRBI both have major role in the clearance of PL and FC of surface remnants in PLTP0 mice. SRBI appears to be dysfunctional in coconut oil diet-fed animals, possibly related to changes in hepatocyte membrane fatty acid composition.
Department of Anatomy and Cell Biology, SUNY Downstate Medical Center, Brooklyn, NY 11203, USA.
Koichi
K
Kawano
Shucun
S
Qin
Claude
C
Vieu
Xavier
X
Collet
Xian-Cheng
XC
Jiang
D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D016466:CHO Cells; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D000074263:Coconut Oil; D006224:Cricetinae; D004042:Dietary Fats, Unsaturated / Q000009:adverse effects; D005260:Female; D008049:Lipase / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010740:Phospholipases / Q000235:genetics / Q000378:metabolism*; D049294:Phospholipid Transfer Proteins; D010743:Phospholipids / Q000378:metabolism*; D010938:Plant Oils / Q000009:adverse effects; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein / Q000235:genetics / Q000378:metabolism*; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
D018955:CD36 Antigens; D002352:Carrier Proteins; D004042:Dietary Fats, Unsaturated; D008565:Membrane Proteins; D049294:Phospholipid Transfer Proteins; D010743:Phospholipids; D010938:Plant Oils; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D002784:Cholesterol; D010740:Phospholipases; D008049:Lipase; D000074263:Coconut Oil