Intermittent hypoxia inhibits clearance of triglyceride-rich lipoproteins and inactivates adipose lipoprotein lipase in a mouse model of sleep apnoea

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorDRAGER, Luciano F.
dc.contributor.authorLI, Jianguo
dc.contributor.authorSHIN, Mi-Kyung
dc.contributor.authorREINKE, Christian
dc.contributor.authorAGGARWAL, Neil R.
dc.contributor.authorJUN, Jonathan C.
dc.contributor.authorBEVANS-FONTI, Shannon
dc.contributor.authorSZTALRYD, Carole
dc.contributor.authorOBYRNE, Sheila M.
dc.contributor.authorKROUPA, Olessia
dc.contributor.authorOLIVECRONA, Gunilla
dc.contributor.authorBLANER, William S.
dc.contributor.authorPOLOTSKY, Vsevolod Y.
dc.date.accessioned2013-07-30T17:52:40Z
dc.date.available2013-07-30T17:52:40Z
dc.date.issued2012
dc.description.abstractDelayed lipoprotein clearance is associated with atherosclerosis. This study examined whether chronic intermittent hypoxia (CIH), a hallmark of obstructive sleep apnoea (OSA), can lead to hyperlipidaemia by inhibiting clearance of triglyceride rich lipoproteins (TRLP). Male C57BL/6J mice on high-cholesterol diet were exposed to 4 weeks of CIH or chronic intermittent air (control). FIO2 was decreased to 6.5 once per minute during the 12 h light phase in the CIH group. After the exposure, we measured fasting lipid profile. TRLP clearance was assessed by oral gavage of retinyl palmitate followed by serum retinyl esters (REs) measurements at 0, 1, 2, 4, 10, and 24 h. Activity of lipoprotein lipase (LpL), a key enzyme of lipoprotein clearance, and levels of angiopoietin-like protein 4 (Angptl4), a potent inhibitor of the LpL activity, were determined in the epididymal fat pads, skeletal muscles, and heart. Chronic intermittent hypoxia induced significant increases in levels of total cholesterol and triglycerides, which occurred in TRLP and LDL fractions (P 0.05 for each comparison). Compared with control mice, animals exposed to CIH showed increases in REs throughout first 10 h after oral gavage of retinyl palmitate (P 0.05), indicating that CIH inhibited TRLP clearance. CIH induced a 5-fold decrease in LpL activity (P 0.01) and an 80 increase in Angptl4 mRNA and protein levels in the epididymal fat, but not in the skeletal muscle or heart. CIH decreases TRLP clearance and inhibits LpL activity in adipose tissue, which may contribute to atherogenesis observed in OSA.
dc.description.indexMEDLINE
dc.description.sponsorshipMid-Atlantic Nutrition Obesity Research Center (NORC) (NIH) [P30 DK072488]
dc.description.sponsorshipConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [200032/2009-7]
dc.description.sponsorshipFundacao Zerbini
dc.description.sponsorshipNational Sleep Foundation/American Lung Association [SF-78568-N]
dc.description.sponsorshipNational Institutes of Health (NIH) [HL07534, R01 HL80105, 5P50HL084945]
dc.description.sponsorshipGerman Research Foundation (DFG) [RE 2842/1-1]
dc.description.sponsorshipSwedish Medical Research Fund [12 203]
dc.description.sponsorshipSwedish Heart and Lung Foundation [20090578]
dc.description.sponsorshipAmerican Heart Association [10GRNT3360001]
dc.description.sponsorshipUnited States Israel Binational Science Foundation [2005265]
dc.identifier.citationEUROPEAN HEART JOURNAL, v.33, n.6, p.783-U33, 2012
dc.identifier.doi10.1093/eurheartj/ehr097
dc.identifier.issn0195-668X
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/1526
dc.language.isoeng
dc.publisherOXFORD UNIV PRESS
dc.relation.ispartofEuropean Heart Journal
dc.rightsrestrictedAccess
dc.rights.holderCopyright OXFORD UNIV PRESS
dc.subjectIntermittent hypoxia
dc.subjectSleep apnoea
dc.subjectDyslipidemia
dc.subjectLipoprotein clearance
dc.subjectAtherosclerosis
dc.subject.otherdiet-induced atherosclerosis
dc.subject.otherangiopoietin-like protein-4
dc.subject.otherpositive airway pressure
dc.subject.otheroxidative stress
dc.subject.otherinsulin-resistance
dc.subject.othergene-expression
dc.subject.otherfatty-acids
dc.subject.otherrisk-factor
dc.subject.othermice
dc.subject.othertissue
dc.subject.wosCardiac & Cardiovascular Systems
dc.titleIntermittent hypoxia inhibits clearance of triglyceride-rich lipoproteins and inactivates adipose lipoprotein lipase in a mouse model of sleep apnoea
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.affiliation.countryAlemanha
hcfmusp.affiliation.countrySuécia
hcfmusp.affiliation.countryEstados Unidos
hcfmusp.affiliation.countryisous
hcfmusp.affiliation.countryisode
hcfmusp.affiliation.countryisose
hcfmusp.author.externalLI, Jianguo:Johns Hopkins Univ, Div Pulm & Crit Care Med, Johns Hopkins Asthma & Allergy Ctr, Sch Med, Baltimore, MD 21224 USA
hcfmusp.author.externalSHIN, Mi-Kyung:Johns Hopkins Univ, Div Pulm & Crit Care Med, Johns Hopkins Asthma & Allergy Ctr, Sch Med, Baltimore, MD 21224 USA
hcfmusp.author.externalREINKE, Christian:Johns Hopkins Univ, Div Pulm & Crit Care Med, Johns Hopkins Asthma & Allergy Ctr, Sch Med, Baltimore, MD 21224 USA; Univ Marburg, Div Pulm Dis, Dept Internal Med, D-35043 Marburg, Germany
hcfmusp.author.externalAGGARWAL, Neil R.:Johns Hopkins Univ, Div Pulm & Crit Care Med, Johns Hopkins Asthma & Allergy Ctr, Sch Med, Baltimore, MD 21224 USA
hcfmusp.author.externalJUN, Jonathan C.:Johns Hopkins Univ, Div Pulm & Crit Care Med, Johns Hopkins Asthma & Allergy Ctr, Sch Med, Baltimore, MD 21224 USA
hcfmusp.author.externalBEVANS-FONTI, Shannon:Johns Hopkins Univ, Div Pulm & Crit Care Med, Johns Hopkins Asthma & Allergy Ctr, Sch Med, Baltimore, MD 21224 USA
hcfmusp.author.externalSZTALRYD, Carole:Univ Maryland, Div Endocrinol, Dept Med, Sch Med, Baltimore, MD 21201 USA
hcfmusp.author.externalOBYRNE, Sheila M.:Columbia Univ, Dept Med, New York, NY 10032 USA
hcfmusp.author.externalKROUPA, Olessia:Umea Univ, Dept Med Biosci, SE-90187 Umea, Sweden
hcfmusp.author.externalOLIVECRONA, Gunilla:Umea Univ, Dept Med Biosci, SE-90187 Umea, Sweden
hcfmusp.author.externalBLANER, William S.:Columbia Univ, Dept Med, New York, NY 10032 USA
hcfmusp.author.externalPOLOTSKY, Vsevolod Y.:Johns Hopkins Univ, Div Pulm & Crit Care Med, Johns Hopkins Asthma & Allergy Ctr, Sch Med, Baltimore, MD 21224 USA
hcfmusp.citation.scopus124
hcfmusp.contributor.author-fmusphcLUCIANO FERREIRA DRAGER
hcfmusp.description.beginpage783
hcfmusp.description.endpageU33
hcfmusp.description.issue6
hcfmusp.description.volume33
hcfmusp.lim.ref2012
hcfmusp.origemWOS
hcfmusp.origem.pubmed21478490
hcfmusp.origem.scopus2-s2.0-84863337923
hcfmusp.origem.wosWOS:000302022600022
hcfmusp.publisher.cityOXFORD
hcfmusp.publisher.countryENGLAND
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hcfmusp.remissive.sponsorshipCNPq
hcfmusp.remissive.sponsorshipFund Zerbini
hcfmusp.remissive.sponsorshipNIH
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