15995171

pubmed:Citation

9

Obese mice without leptin (ob/ob) or the leptin receptor (db/db) have increased plasma HDL levels and accumulate a unique lipoprotein referred to as LDL/HDL1. To determine the role of apolipoprotein A-I (apoA-I) in the formation and accumulation of LDL/HDL1, both ob/ob and db/db mice were crossed onto an apoA-I-deficient (apoA-I(-/-)) background. Even though the obese apoA-I(-/-) mice had an expected dramatic decrease in HDL levels, the LDL/HDL1 particle persisted. The cholesterol in this lipoprotein range was associated with both alpha- and beta-migrating particles, confirming the presence of small LDLs and large HDLs. Moreover, in the obese apoA-I(-/-) mice, LDL particles were smaller and HDLs were more negatively charged and enriched in apoE compared with controls. This LDL/HDL1 particle was rapidly remodeled to the size of normal HDL after injection into C57BL/6 mice, but it was not catabolized in obese apoA-I(-/-) mice even though plasma hepatic lipase (HL) activity was increased significantly. The finding of decreased hepatic scavenger receptor class B type I (SR-BI) protein levels may explain the persistence of LDL/HDL1 in obese apoA-I(-/-) mice. Our studies suggest that the maturation and removal of large HDLs depends on the integrity of a functional axis of apoA-I, HL, and SR-BI. Moreover, the presence of large HDLs without apoA-I provides evidence for an apoA-I-independent pathway of cholesterol efflux, possibly sustained by apoE.

eng

IM

MEDLINE

0022-2275

Print

NLM

2007-14

pubmed-meshheading:15995171-Animals, pubmed-meshheading:15995171-Antigens, CD36, pubmed-meshheading:15995171-Apolipoprotein A-I, pubmed-meshheading:15995171-Crosses, Genetic, pubmed-meshheading:15995171-Gene Expression, pubmed-meshheading:15995171-Lipase, pubmed-meshheading:15995171-Lipoproteins, pubmed-meshheading:15995171-Lipoproteins, HDL, pubmed-meshheading:15995171-Lipoproteins, LDL, pubmed-meshheading:15995171-Liver, pubmed-meshheading:15995171-Mice, pubmed-meshheading:15995171-Mice, Inbred C57BL, pubmed-meshheading:15995171-Mice, Knockout, pubmed-meshheading:15995171-Obesity, pubmed-meshheading:15995171-Particle Size, pubmed-meshheading:15995171-RNA, Messenger, pubmed-meshheading:15995171-Receptors, Immunologic, pubmed-meshheading:15995171-Receptors, Scavenger, pubmed-meshheading:15995171-Scavenger Receptors, Class B

Persistence of high density lipoprotein particles in obese mice lacking apolipoprotein A-I.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural