Scavenger receptor class B type I mediates the selective uptake of high-density lipoprotein-associated cholesteryl ester by the liver in mice.
OBJECTIVE
High-density lipoprotein (HDL) cholesteryl esters (CE) are taken up by liver and adrenals selectively, ie, independent from particle internalization. Class B type I scavenger receptor (SR-BI) mediates this uptake in vitro. The role of SR-BI in HDL metabolism was explored in mice.


RESULTS
Mice with a mutation in the SR-BI gene (SR-BI KO) and wild-type (WT) littermates were used. Mutants had increased HDL cholesterol. HDL was labeled with 125I (protein) and [3H] (CE). After HDL injection, blood samples were drawn and finally the mice were euthanized. In WT, the plasma decay of HDL-associated [3H] is faster compared with 125I and this represents whole-body selective CE uptake. In SR-BI KO, the decay of both tracers is similar, yielding no selective CE removal. In WT liver and adrenals, uptake of [3H] is higher than 125I, showing selective uptake. In SR-BI KO, liver uptake of [3H] and 125I are similar, proposing no selective HDL CE uptake. In SR-BI KO adrenals, selective uptake is reduced; however, even in the absence of SR-BI, this uptake is detected using WT-HDL.


CONCLUSIONS
SR-BI mediates selective uptake of HDL CE by the liver. In adrenals, an alternative mechanism or mechanisms can play a role in selective CE uptake.
Brundert
May
M
University Hospital Hamburg-Eppendorf, Hamburg, Germany.
Ewert
Anne
A
Heeren
Joerg
J
Behrendt
Barbara
B
Ramakrishnan
Rajasekhar
R
Greten
Heiner
H
Merkel
Martin
M
Rinninger
Franz
F
D000818:Animals; D018955:CD36 Antigens; D002788:Cholesterol Esters / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B
D018955:CD36 Antigens; D002788:Cholesterol Esters; D008076:Cholesterol, HDL; D008075:Lipoproteins, HDL; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B