Tissue-specific induction of apoE expression in vivo by
LXR ligands. (A) Sterol-induced expression of apoE in
macrophages requires LXR. Peritoneal macrophages were isolated as
described in Materials and Methods and cultured for
42 h in the presence of 100 μM mevalonic acid (control) or
mevalonic acid plus 5 μM compactin (unloaded), 10 μM
22(R)-hydroxycholesterol [22(R)HC], or
10 μM T0901317. (B and C) LXR and RXR
ligands induce apoE expression in an LXR-dependent manner in adipose
tissue (B) but not in liver (C).
Wild-type or Lxrα/β−/− mice were fed ad
libitum diets containing 0.2% cholesterol and vehicle (Veh),
LXR agonist (T0901317, 50 mg/kg body weight) or RXR-specific agonist
(LG268, 30 mg/kg body weight) for 10 days. Northern analysis was
performed as above. Blots were quantitated by PhosphorImager,
standardized against actin or cyclophilin (cyclo), and mathematically
adjusted to establish a unit of 1 for the wild-type group receiving
vehicle.