title: Possibility of increasing cholesterol efflux by adiponectin and its receptors through the ATP binding cassette transporter A1 in HEK293T cells.
abstract: A decrease in adiponectin secretion leads to the early stage of atherosclerosis. Discoidal high-density lipoproteins (HDL) accept the cholesterol that effluxes from cells expressing the ATP binding cassette transporter A1 (ABCA1) in the first step of reverse cholesterol transport (RCT). Recently, a new therapeutic strategy involving reconstituted (r)HDL has been shown to enhance RCT. Therefore, we hypothesized that adiponectin may increase the efflux associated with ABCA1 and also enhance rHDL-induced efflux in human embryonic kidney 293 (HEK293T) cells. We transfected adiponectin receptor 1 and 2 (AdipoR1 and AdipoR2) cDNA into cells. The transfected cells were labeled with [(3)H]cholesterol following cholesterol loading with or without adiponectin for 24h. The levels of cholesterol efflux were analyzed using a liquid scintillation counter. Treatment with adiponectin was associated with significantly higher levels of efflux in AdipoR1- and AdipoR2-transfected cells. Interestingly, rHDL-induced cholesterol efflux was enhanced in the presence of adiponectin. The down-regulation of adiponectin receptors using short-hairpin RNA decreased rHDL-induced cholesterol efflux with the down-regulation of ABCA1. In summary, adiponectin and its receptors increased cholesterol efflux and also enhanced rHDL-induced efflux at least partially through an ABCA1 pathway. These results suggest that adiponectin may enhance the RCT system and induce an anti-atherogenic effect.
authors: Department of Cardiology, Fukuoka University School of Medicine, Fukuoka, Japan.
authors: Ken
authors: K
authors: Kitajima
authors: Shin-ichiro
authors: S
authors: Miura
authors: Toshimasa
authors: T
authors: Yamauchi
authors: Yoshinari
authors: Y
authors: Uehara
authors: Yoshihiro
authors: Y
authors: Kiya
authors: Kerry-Anne
authors: KA
authors: Rye
authors: Takashi
authors: T
authors: Kadowaki
authors: Keijiro
authors: K
authors: Saku
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D052242:Adiponectin / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D054419:Receptors, Adiponectin / Q000235:genetics / Q000378:metabolism*; D051122:Scavenger Receptors, Class B / Q000378:metabolism
chemical_list: C577836:ABCA1 protein, human; C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D052242:Adiponectin; D054419:Receptors, Adiponectin; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D002784:Cholesterol