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Lipids

, Volume 49, Issue 6, pp 505–515 | Cite as

Lipidomic Analyses of Female Mice Lacking Hepatic Lipase and Endothelial Lipase Indicate Selective Modulation of Plasma Lipid Species

  • Yanbo Yang
  • Takashi Kuwano
  • William R. Lagor
  • Carolyn J. Albert
  • Siobhan Brenton
  • Daniel J. Rader
  • David A. Ford
  • Robert J. BrownEmail author
Original Article

Abstract

Hepatic lipase (HL) and endothelial lipase (EL) share overlapping and complementary roles in lipoprotein metabolism. The deletion of HL and EL alleles in mice raises plasma total cholesterol and phospholipid concentrations. However, the influence of HL and EL in vivo on individual molecular species from each class of lipid is not known. We hypothesized that the loss of HL, EL, or both in vivo may affect select molecular species from each class of lipids. To test this hypothesis, we performed lipidomic analyses on plasma and livers from fasted female wild-type, HL-knockout, EL-knockout, and HL/EL-double knockout mice. Overall, the loss of HL, EL, or both resulted in minimal changes to hepatic lipids; however, select species of CE were surprisingly reduced in the livers of mice only lacking EL. The loss of HL, EL, or both reduced the plasma concentrations for select molecular species of triacylglycerol, diacylglycerol, and free fatty acid. On the other hand, the loss of HL, EL, or both raised the plasma concentrations for select molecular species of phosphatidylcholine, cholesteryl ester, diacylglycerol, sphingomyelin, ceramide, plasmanylcholine, and plasmenylcholine. The increased plasma concentration of select ether phospholipids was evident in the absence of EL, thus suggesting that EL might exhibit a phospholipase A2 activity. Using recombinant EL, we showed that it could hydrolyse the artificial phospholipase A2 substrate 4-nitro-3-(octanoyloxy)benzoic acid. In summary, our study shows for the first time the influence of HL and EL on individual molecular species of several classes of lipids in vivo using lipidomic methods.

Keywords

Lipoproteins Hepatic lipase Endothelial lipase Knockout mice Lipidomics Mass spectrometry Phospholipase A2 

Abbreviations

CE

Cholesteryl ester

Cer

Ceramide

CerPCho

Sphingomyelin

DAG

Diacylglycerol

dko

Double knockout

EL

Endothelial lipase

ESI–MS

Electrospray ionization-mass spectrometry

FFA

Free fatty acid

HDL

High-density lipoprotein

HDL-C

High-density lipoprotein cholesterol

HL

Hepatic lipase

ko

Knockout

LPL

Lipoprotein lipase

LysoPtdCho

Lysophosphatidylcholine

NL

Neutral loss

NOB

4-Nitro-3-(octanoyloxy)benzoic acid

PakCho

Plasmanylcholine

PLA2

Phospholipase A2

PlsCho

Plasmenylcholine

PtdCho

Phosphatidylcholine

PL

Phospholipid

sdLDL

Small-dense low-density lipoprotein

SRM

Selective reaction monitoring

TAG

Triacylglycerol

WT

Wild-type

Notes

Acknowledgments

This work was supported in part by an IgniteR&D grant from the Research & Development Corporation of Newfoundland and Labrador (R.J.B.), a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada (R.J.B.), a National Scientist Development Grant (#11SDG7210077) from the American Heart Association (W.R.L.), National Institutes of Health Grants HL-022633 and HL-055323 (D.J.R.), and National Institutes of Health Grants HL-074214 and HL-111906 (D.A.F.). The authors wish to thank Ms. Catherine Wright (University of Washington, Seattle, WA, USA) for advice with statistical analyses.

Supplementary material

11745_2014_3907_MOESM1_ESM.pdf (505 kb)
Supplementary material 1 (PDF 505 kb)

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Copyright information

© AOCS 2014

Authors and Affiliations

  • Yanbo Yang
    • 1
  • Takashi Kuwano
    • 2
  • William R. Lagor
    • 2
  • Carolyn J. Albert
    • 3
  • Siobhan Brenton
    • 1
  • Daniel J. Rader
    • 2
  • David A. Ford
    • 3
  • Robert J. Brown
    • 1
    Email author
  1. 1.Department of BiochemistryMemorial University of NewfoundlandSt. John’sCanada
  2. 2.Institute for Translational Medicine and Therapeutics, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  3. 3.Department of Biochemistry and Molecular Biology, School of Medicine, and Center for Cardiovascular ResearchSaint Louis UniversitySt. LouisUSA

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