出版社：American Society for Biochemistry and Molecular Biology
摘要：The process of cholesterol absorption has yet to be completelydefined at the molecular level. Because of its ability to esterifycholesterol for packaging into nascent chylomicrons, ACAT2 playsan important role in cholesterol absorption. However, it hasbeen found that cholesterol absorption is not completely inhibitedin ACAT2-deficient (ACAT2 KO) mice. Because ABCA1 mRNA expressionwas increased 3-fold in the small intestine of ACAT2 KO mice,we hypothesized that ABCA1-dependent cholesterol efflux sustainscholesterol absorption in the absence of ACAT2. To test thishypothesis, cholesterol absorption was measured in mice deficientin both ABCA1 and ACAT2 (DKO). Compared with wild-type, ABCA1KO, or ACAT2 KO mice, DKO mice displayed the lowest level ofcholesterol absorption. The concentrations of hepatic free andesterified cholesterol and gallbladder bile cholesterol weresignificantly reduced in DKO compared with wild-type and ABCA1KO mice, although these measures of hepatic cholesterol metabolismwere very similar in DKO and ACAT2 KO mice.
We conclude that ABCA1, especially in the absence of ACAT2,can have a significant effect on cholesterol absorption, althoughACAT2 has a more substantial role in this process than ABCA1.Abbreviations: apoB, apolipoprotein B; DKO, deficient in both ABCA1 and ACAT2; KO, -deficient; LXR, liver X receptor; NPC1L1, Niemann-Pick C1-like 1; SR-BI, scavenger receptor class B type I; TPC, plasma total cholesterol
Supplementary key words Niemann-Pick C1-like 1 • ATP-binding cassette transporter G5 • gallbladder bile • liver • plasma lipoproteins • ATP binding cassette transporter A1 • acyl-coenzyme A:cholesterol acyltransferase
