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

Marnie L. Gruen, Michelle R. Plummer, Wenwu Zhang, Kelly A. Posey, MacRae F. Linton, Sergio Fazio, Alyssa H. Hasty

    Research output: Contribution to journalArticle

    22 Scopus citations

    Abstract

    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 α- and β-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.

    Original languageEnglish (US)
    Pages (from-to)2007-2014
    Number of pages8
    JournalJournal of lipid research
    Volume46
    Issue number9
    DOIs
    StatePublished - Sep 2005

    Keywords

    • Hepatic lipase
    • Obesity
    • Remodeling
    • Scavenger receptor class B type I
    • Small, dense low density lipoproteins

    ASJC Scopus subject areas

    • Biochemistry
    • Endocrinology
    • Cell Biology

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    Gruen, M. L., Plummer, M. R., Zhang, W., Posey, K. A., Linton, M. F., Fazio, S., & Hasty, A. H. (2005). Persistence of high density lipoprotein particles in obese mice lacking apolipoprotein A-I. Journal of lipid research, 46(9), 2007-2014. https://doi.org/10.1194/jlr.M500181-JLR200