An antibody blocking CETP-mediated lipid transfer sharply cuts HDL cholesteryl ester uptake by human adipocytes, revealing a direct CETP-dependent route into fat cells (J Biol Chem 1997)

Original title: Cholesteryl ester transfer protein mediates selective uptake of high density lipoprotein cholesteryl esters by human adipose tissue

J Biol Chem · 19 September 1997 · 9

Benoist F, Lau P, McDonnell M, Doelle H, Milne R, McPherson R

Using organ culture and collagenase-digested human adipocytes, the authors examined the role of CETP in selective uptake of HDL-derived cholesteryl esters (CE) by adipose tissue. Incubating tissue with HDL containing [3H]CE or 125I-apoA-I produced significant HDL-CE-derived label uptake, which increased dose-dependently with recombinant CETP (rCETP), while apoA-I uptake and degradation were unaffected by rCETP. The anti-CETP monoclonal antibody TP2, which inhibits neutral lipid transfer, markedly reduced selective HDL-CE uptake. Isolated adipocytes showed the same selective HDL-CE uptake enhanced by rCETP, accompanied by decreased medium HDL-CE and increased HDL free cholesterol, an effect attenuated by TP2, with no significant changes in phospholipid, apoA-I, or apoA-II. These data demonstrate a novel role for CETP in selective HDL cholesteryl ester uptake by human adipocytes, physiologically significant for HDL remodeling and cholesterol accumulation.

Original abstract

We have determined the role of cholesteryl ester transfer protein (CETP) in selective uptake of high density lipoprotein (HDL)-derived cholesteryl esters (CE) by human adipose tissue, using organ culture or collagenase-digested adipocytes. Incubation of the fresh tissue fragments with HDL containing [3H]CE or 125I-apoprotein (apo) A-I resulted in significant uptake of HDL-CE-derived label. Addition of recombinant CETP (rCETP) increased CE uptake in a dose-response fashion. In contrast, little association of 125I-apoA-I with adipose tissue was noted, and addition of rCETP did not alter apoA-I uptake or degradation. Incubation of adipose tissue with TP2, an anti-CETP monoclonal antibody, which inhibits neutral lipid transfer, markedly reduced selective uptake of HDL-CE. Studies using human adipocytes isolated by collagenase digestion also demonstrated selective uptake of HDL-CE and enhancement of this process by rCETP. To confirm that the association of HDL-CE-derived radioactivity with adipose tissue was not due to neutral lipid exchange between adipocytes and HDL, we measured changes in HDL composition following incubation of HDL and rCETP with isolated adipocytes. A decrease in HDL-CE concentration in the medium was observed, an effect which was markedly attenuated when incubations were carried out in the presence of monoclonal antibody TP2. Furthermore, the decrease in HDL-CE was accompanied by an increase in HDL free cholesterol, likely representing efflux of adipocyte cholesterol to HDL. There were no significant changes in phospholipid, apoA-I, or apoA-II in the medium following incubation with adipocytes. These data demonstrate a novel and important role for CETP in selective uptake of HDL-cholesteryl esters by human adipocytes and suggest that this pathway may be of quantitative physiological significance in HDL remodeling and adipocyte cholesterol accumulation.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.