title: Intermittent hypoxia inhibits clearance of triglyceride-rich lipoproteins and inactivates adipose lipoprotein lipase in a mouse model of sleep apnoea.
abstract: OBJECTIVE
  Delayed 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).
  
  
  RESULTS
  Male C57BL/6J mice on high-cholesterol diet were exposed to 4 weeks of CIH or chronic intermittent air (control). FIO(2) 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.
  
  
  CONCLUSIONS
  CIH decreases TRLP clearance and inhibits LpL activity in adipose tissue, which may contribute to atherogenesis observed in OSA.
authors.affiliation: Division of Pulmonary and Critical Care Medicine,  Johns Hopkins University School of Medicine, Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224,  USA.
authors.forename: Luciano F
authors.initials: LF
authors.lastname: Drager
authors.forename: Jianguo
authors.initials: J
authors.lastname: Li
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Shin
authors.forename: Christian
authors.initials: C
authors.lastname: Reinke
authors.forename: Neil R
authors.initials: NR
authors.lastname: Aggarwal
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Jun
authors.forename: Shannon
authors.initials: S
authors.lastname: Bevans-Fonti
authors.forename: Carole
authors.initials: C
authors.lastname: Sztalryd
authors.forename: Sheila M
authors.initials: SM
authors.lastname: O'Byrne
authors.forename: Olessia
authors.initials: O
authors.lastname: Kroupa
authors.forename: Gunilla
authors.initials: G
authors.lastname: Olivecrona
authors.forename: William S
authors.initials: WS
authors.lastname: Blaner
authors.forename: Vsevolod Y
authors.initials: VY
authors.lastname: Polotsky
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002914:Chylomicrons / Q000378:metabolism; D004036:Diet, Atherogenic; D000860:Hypoxia / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020181:Sleep Apnea, Obstructive / Q000209:etiology / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; C407088:Angptl4 protein, mouse; D001786:Blood Glucose; D002914:Chylomicrons; D007328:Insulin; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D014280:Triglycerides; C030087:lipoprotein triglyceride; D008071:Lipoprotein Lipase