Liver-specific overexpression of scavenger receptor BI decreases levels of very low density lipoprotein ApoB, low density lipoprotein ApoB, and high density lipoprotein in transgenic mice.
Scavenger receptor BI (SR-BI) is known to mediate the selective uptake of high density lipoprotein (HDL) cholesteryl ester (CE) in liver and steroidogenic tissues. To evaluate the role of SR-BI in plasma lipoprotein metabolism, we have generated transgenic mice with liver-specific overexpression of murine SR-BI. On a chow diet SR-BI transgenic (SR-BI Tg) mice have decreased HDL-CE, apoA-I, and apoA-II levels; plasma triglycerides, low density lipoprotein (LDL) cholesterol, and very low density lipoprotein (VLDL) and LDL apoB were also decreased, compared with control mice. Turnover studies using non-degradable CE and protein labels showed markedly increased total and selective uptake of HDL-CE in the liver and increased HDL protein catabolism in both liver and kidney. To evaluate the changes in apoB further, mice were challenged with high fat, high cholesterol diets. In SR-BI Tg mice plasma apoB levels were only 3-15% of control levels, and the dietary increase in VLDL and LDL apoB was virtually abolished. These studies show that steady state overexpression of hepatic SR-BI reduces HDL levels and increases reverse cholesterol transport. They also indicate that SR-BI can play a role in the metabolism of apoB-containing lipoproteins. The dual effects of increased reverse cholesterol transport and lowering of apoB-containing lipoproteins that result from hepatic SR-BI overexpression could have anti-atherogenic consequences.
Wang
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Division of Molecular Medicine, Department of Medicine, Columbia University, New York, New York 10032, USA.
Arai
T
T
Ji
Y
Y
Rinninger
F
F
Tall
A R
AR
D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism*; D018955:CD36 Antigens; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D004041:Dietary Fats / Q000008:administration & dosage; D005260:Female; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
D001055:Apolipoproteins B; D018955:CD36 Antigens; D002791:Cholesterol, Dietary; D004041:Dietary Fats; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D007862:Phosphatidylcholine-Sterol O-Acyltransferase