Possibility of increasing cholesterol efflux by adiponectin and its receptors through the ATP binding cassette transporter A1 in HEK293T cells

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• 作者：Ken Kitajima^a ; Shin-ichiro Miura^a ; ^{miuras@cis.fukuoka-u.ac.jp" rel="nofollow} ; Toshimasa Yamauchi^b ; Yoshinari Uehara^a ; Yoshihiro Kiya^a ; Kerry-Anne Rye^c ; Takashi Kadowaki^b ; Keijiro Saku^a
• 关键词：AdipoR1 ; AdipoR2 ; Cholesterol efflux ; ABCA1 ; rHDL
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2011
• 出版时间：29 July 2011
• 年：2011
• 卷：411
• 期：2
• 页码：305-311
• 全文大小：384 K

文摘

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 [³H]cholesterol following cholesterol loading with or without adiponectin for 24 h. 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.