Hepatic lipase- and endothelial lipase-deficiency in mice promotes macrophage-to-feces RCT and HDL antioxidant properties

Joan Carles Escolà-Gil, Xiangyu Chen, Josep Julve, Helena Quesada, David Santos, Jari Metso, Monica Tous, Matti Jauhiainen, Francisco Blanco-Vaca

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20 Citations (Scopus)


Hepatic lipase (HL) and endothelial lipase (EL) are negative regulators of plasma HDL cholesterol (HDLc) levels and presumably could affect two main HDL atheroprotective functions, macrophage-to-feces reverse cholesterol transport (RCT) and HDL antioxidant properties. In this study, we assessed the effects of both HL and EL deficiency on macrophage-specific RCT process and HDL ability to protect against LDL oxidation. HL- and EL-deficient and wild-type mice were injected intraperitoneally with [3H]cholesterol-labeled mouse macrophages, after which the appearance of [3H]cholesterol in plasma, liver, and feces was determined. The degree of HDL oxidation and the protection of oxidative modification of LDL co-incubated with HDL were evaluated by measuring conjugated diene kinetics. Plasma levels of HDLc, HDL phospholipids, apoA-I, and platelet-activated factor acetyl-hydrolase were increased in both HL- and EL-deficient mice. These genetically modified mice displayed increased levels of radiolabeled, HDL-bound [3H]cholesterol 48 h after the label injection. The magnitude of macrophage-derived [3H]cholesterol in feces was also increased in both the HL- and EL-deficient mice. HDL from the HL- and EL-deficient mice was less prone to oxidation and had a higher ability to protect LDL from oxidation, compared with the HDL derived from the wild-type mice. These changes were correlated with plasma apoA-I and apoA-I/HDL total protein levels. In conclusion, targeted inactivation of both HL and EL in mice promoted macrophage-to-feces RCT and enhanced HDL antioxidant properties. © 2013 Elsevier B.V.
Original languageEnglish
Pages (from-to)691-697
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Issue number4
Publication statusPublished - 1 Apr 2013


  • apoA-I
  • Endothelial lipase
  • HDL
  • Hepatic lipase
  • Oxidation
  • Reverse cholesterol transport


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