Acute hypoxia induces hypertriglyceridemia by decreasing plasma triglyceride clearance in mice

dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorJUN, Jonathan C.
dc.contributor.authorSHIN, Mi-Kyung
dc.contributor.authorYAO, Qiaoling
dc.contributor.authorBEVANS-FONTI, Shannon
dc.contributor.authorPOOLE, James
dc.contributor.authorDRAGER, Luciano F.
dc.contributor.authorPOLOTSKY, Vsevolod Y.
dc.date.accessioned2013-07-30T17:52:32Z
dc.date.available2013-07-30T17:52:32Z
dc.date.issued2012
dc.description.abstractObstructive sleep apnea (OSA) induces intermittent hypoxia (IH) during sleep and is associated with elevated triglycerides (TG). We previously demonstrated that mice exposed to chronic IH develop elevated TG. We now hypothesize that a single exposure to acute hypoxia also increases TG due to the stimulation of free fatty acid (FFA) mobilization from white adipose tissue (WAT), resulting in increased hepatic TG synthesis and secretion. Male C57BL6/J mice were exposed to FiO(2) = 0.21, 0.17, 0.14, 0.10, or 0.07 for 6 h followed by assessment of plasma and liver TG, glucose, FFA, ketones, glycerol, and catecholamines. Hypoxia dose-dependently increased plasma TG, with levels peaking at FiO(2) = 0.07. Hepatic TG levels also increased with hypoxia, peaking at FiO(2) = 0.10. Plasma catecholamines also increased inversely with FiO(2). Plasma ketones, glycerol, and FFA levels were more variable, with different degrees of hypoxia inducing WAT lipolysis and ketosis. FiO(2) = 0.10 exposure stimulated WAT lipolysis but decreased the rate of hepatic TG secretion. This degree of hypoxia rapidly and reversibly delayed TG clearance while decreasing [H-3]triolein-labeled Intralipid uptake in brown adipose tissue and WAT. Hypoxia decreased adipose tissue lipoprotein lipase (LPL) activity in brown adipose tissue and WAT. In addition, hypoxia decreased the transcription of LPL, peroxisome proliferator-activated receptor-gamma, and fatty acid transporter CD36. We conclude that acute hypoxia increases plasma TG due to decreased tissue uptake, not increased hepatic TG secretion.
dc.description.indexMEDLINE
dc.description.sponsorshipEudowood Foundation [80026999]
dc.description.sponsorshipJohns Hopkins Clinician Scientist Award [80028014]
dc.description.sponsorshipNIH/National Heart, Lung, and Blood Institute [T32 HL-07534, R01 HL-080105, P50 HL-084945]
dc.description.sponsorshipAmerican Lung Association-National Sleep Foundation Pickwick Fellowship [SF-78568-N]
dc.description.sponsorshipAmerican Heart Association [10GRNT3360001]
dc.identifier.citationAMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, v.303, n.3, p.E377-E388, 2012
dc.identifier.doi10.1152/ajpendo.00641.2011
dc.identifier.issn0193-1849
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/1482
dc.language.isoeng
dc.publisherAMER PHYSIOLOGICAL SOC
dc.relation.ispartofAmerican Journal of Physiology-Endocrinology and Metabolism
dc.rightsrestrictedAccess
dc.rights.holderCopyright AMER PHYSIOLOGICAL SOC
dc.subjectlipolysis
dc.subjectlipases
dc.subjectadipose
dc.subjectthermoregulation
dc.subjectmetabolism
dc.subject.otherchronic intermittent hypoxia
dc.subject.otherobstructive sleep-apnea
dc.subject.otherhigh-altitude exposure
dc.subject.otheractivated protein-kinase
dc.subject.otherhormone-sensitive lipase
dc.subject.otherbrown adipose-tissue
dc.subject.otherlipoprotein-lipase
dc.subject.othergene-expression
dc.subject.otherlipid-metabolism
dc.subject.otheradipocyte differentiation
dc.subject.wosEndocrinology & Metabolism
dc.subject.wosPhysiology
dc.titleAcute hypoxia induces hypertriglyceridemia by decreasing plasma triglyceride clearance in mice
dc.typearticle
dc.type.categoryoriginal article
dc.type.versionpublishedVersion
dspace.entity.typePublication
hcfmusp.affiliation.countryEstados Unidos
hcfmusp.affiliation.countryisous
hcfmusp.author.externalJUN, Jonathan C.:Johns Hopkins Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21224 USA
hcfmusp.author.externalSHIN, Mi-Kyung:Johns Hopkins Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21224 USA
hcfmusp.author.externalYAO, Qiaoling:Johns Hopkins Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21224 USA
hcfmusp.author.externalBEVANS-FONTI, Shannon:Johns Hopkins Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21224 USA
hcfmusp.author.externalPOOLE, James:Johns Hopkins Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21224 USA
hcfmusp.author.externalPOLOTSKY, Vsevolod Y.:Johns Hopkins Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21224 USA
hcfmusp.citation.scopus68
hcfmusp.contributor.author-fmusphcLUCIANO FERREIRA DRAGER
hcfmusp.description.beginpageE377
hcfmusp.description.endpageE388
hcfmusp.description.issue3
hcfmusp.description.volume303
hcfmusp.lim.ref2012
hcfmusp.origemWOS
hcfmusp.origem.pubmed22621867
hcfmusp.origem.scopus2-s2.0-84864522443
hcfmusp.origem.wosWOS:000307228700008
hcfmusp.publisher.cityBETHESDA
hcfmusp.publisher.countryUSA
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