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 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Obese Mice
Apolipoprotein A-I
HDL Lipoproteins
CD36 Antigens
Apolipoproteins E
Lipase
Lipoproteins
Liver
Cholesterol
Plasmas
Leptin Receptors
Leptin
Inbred C57BL Mouse
oxidized low density lipoprotein
Injections

Keywords

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

ASJC Scopus subject areas

  • Endocrinology

Cite this

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

Persistence of high density lipoprotein particles in obese mice lacking apolipoprotein A-I. / Gruen, Marnie L.; Plummer, Michelle R.; Zhang, Wenwu; Posey, Kelly A.; Linton, MacRae F.; Fazio, Sergio; Hasty, Alyssa H.

In: Journal of Lipid Research, Vol. 46, No. 9, 09.2005, p. 2007-2014.

Research output: Contribution to journalArticle

Gruen, Marnie L. ; Plummer, Michelle R. ; Zhang, Wenwu ; Posey, Kelly A. ; Linton, MacRae F. ; Fazio, Sergio ; Hasty, Alyssa H. / Persistence of high density lipoprotein particles in obese mice lacking apolipoprotein A-I. In: Journal of Lipid Research. 2005 ; Vol. 46, No. 9. pp. 2007-2014.
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AU - Fazio, Sergio

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AB - 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.

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