Apolipoprotein A-I carboxy-terminal domain residues 187–243 are required for adiponectin-induced cholesterol efflux

Adiponectin exerts its atheroprotection by stimulating adenosine triphosphate binding cassette transporter A1 (ABCA1)-mediated cholesterol efflux to apolipoprotein A-I (apoA-I). However, involvement of the apoA-I residues in this process have not been studied. In Tamm-Horsfall 1 (THP-1) macrophages and baby hamster kidney (BHK) cells we assessed adiponectin's potential to restore cholesterol efflux in the presence of apoA-I and ABCA1 mutants, respectively. Adiponectin was unable to restore efflux from THP-1 macrophages in the presence of apoA-I carboxy-terminal domain (CTD) successive mutants from residues 187–243 versus apoA-I mutants alone. Furthermore, adiponectin did not significantly influence cholesterol efflux to apoA-I from BHK-ABCA1 mutant cells. Adiponectin appears to require functional apoA-I CTD residues 187–243 and wild-type ABCA1 to mediate efficient cholesterol efflux from THP-1 macrophages and BHK cells, respectively. Therefore, adiponectin cannot rescue defective cholesterol efflux in apoA-I- or ABCA1-mutant conditions, but rather increases cholesterol efflux in wild-type apoA-I conditions compared to apoA-I exposure alone. •ApoA-I CTD residues 187–243 are required for ABCA1-mediated cholesterol efflux in macrophages.•Adiponectin is unable to recover cholesterol efflux during apoA-I CTD mutations.•Adiponectin did not influence cholesterol efflux in mutated ABCA1 baby hamster kidney cells.•Adiponectin requires functional apoA-I CTD and ABCA1 to increase cholesterol efflux.