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

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Citações na Scopus
122
Tipo de produção
article
Data de publicação
2012
Título da Revista
ISSN da Revista
Título do Volume
Editora
OXFORD UNIV PRESS
Autores
LI, Jianguo
SHIN, Mi-Kyung
REINKE, Christian
AGGARWAL, Neil R.
JUN, Jonathan C.
BEVANS-FONTI, Shannon
SZTALRYD, Carole
OBYRNE, Sheila M.
KROUPA, Olessia
Citação
EUROPEAN HEART JOURNAL, v.33, n.6, p.783-U33, 2012
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
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). 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.
Palavras-chave
Intermittent hypoxia, Sleep apnoea, Dyslipidemia, Lipoprotein clearance, Atherosclerosis
Referências
  1. AaltoSetala K, 1996, J LIPID RES, V37, P1802
  2. Drager LF, 2010, PLOS ONE, V5, DOI 10.1371/journal.pone.0012065
  3. Flemons WW, 1999, SLEEP, V22, P667
  4. ANTRAS J, 1991, MOL CELL ENDOCRINOL, V82, P183, DOI 10.1016/0303-7207(91)90030-V
  5. Augustus AS, 2006, J BIOL CHEM, V281, P8716, DOI 10.1074/jbc.M509890200
  6. Belanger AJ, 2002, J MOL CELL CARDIOL, V34, P765, DOI 10.1006/jmcc.2002.2021
  7. BLANER WS, 1994, J BIOL CHEM, V269, P16559
  8. Casanovas A, 2007, J LIPID RES, V48, P863, DOI 10.1194/jlr.M600487-JLR200
  9. Clee SM, 2000, J LIPID RES, V41, P521
  10. Cuhadaroglu C, 2009, LUNG, V187, P75, DOI 10.1007/s00408-008-9131-5
  11. Deguchi JO, 2009, ARTERIOSCL THROM VAS, V29, P1664, DOI 10.1161/ATVBAHA.109.194043
  12. Dicker A, 2007, HORM METAB RES, V39, P282, DOI 10.1055/s-2007-973812
  13. Drager LF, 2007, AM J RESP CRIT CARE, V176, P706, DOI 10.1164/rccm.200703-500OC
  14. Drager LF, 2011, CHEST, V140, P534, DOI 10.1378/chest.10-2223
  15. Drager LF, 2010, ATHEROSCLEROSIS, V208, P490, DOI 10.1016/j.atherosclerosis.2009.08.016
  16. Drager LF, 2010, CURR OPIN ENDOCRINOL, V17, P161, DOI 10.1097/MED.0b013e3283373624
  17. Fletcher EC, 2003, SLEEP, V26, P15
  18. FRIED SK, 1987, INT J OBESITY, V11, P129
  19. Georgiadi A, 2010, CIRC RES, V106, P1712, DOI 10.1161/CIRCRESAHA.110.217380
  20. Hausman Dorothy B., 2008, V456, P201, DOI 10.1007/978-1-59745-245-8_15
  21. Iesato K, 2007, CIRC J, V71, P1293, DOI 10.1253/circj.71.1293
  22. Iiyori N, 2007, AM J RESP CRIT CARE, V175, P851, DOI 10.1164/rccm.200610-1527OC
  23. ISHIBASHI S, 1993, J CLIN INVEST, V92, P883, DOI 10.1172/JCI116663
  24. Jackson DE, 2003, FEBS LETT, V540, P7, DOI 10.1016/S0014-5793(03)00224-2
  25. Jelic S, 2008, CIRCULATION, V117, P2270, DOI 10.1161/CIRCULATIONAHA.107.741512
  26. Jun J, 2010, ATHEROSCLEROSIS, V209, P381, DOI 10.1016/j.atherosclerosis.2009.10.017
  27. Kim JB, 1996, GENE DEV, V10, P1096, DOI 10.1101/gad.10.9.1096
  28. Li JG, 2005, J APPL PHYSIOL, V99, P1643, DOI 10.1152/japplphysiol.00522.2005
  29. Li JG, 2006, PHYSIOL GENOMICS, V25, P450, DOI 10.1152/physiolgenomics.00293.2005
  30. Li JG, 2007, J APPL PHYSIOL, V102, P557, DOI 10.1152/japplphysiol.01081.2006
  31. Li JG, 2005, CIRC RES, V97, P698, DOI 10.1161/01.RES.000018379.60089.a9
  32. Lichtenstein L, 2010, BBA-MOL CELL BIOL L, V1801, P415, DOI 10.1016/j.bbalip.2009.12.015
  33. Mahley RW, 2007, J CLIN INVEST, V117, P94, DOI 10.1172/JCI30889
  34. Manalo DJ, 2005, BLOOD, V105, P659, DOI 10.1182/blood-2004-07-2958
  35. Mandard S, 2006, J BIOL CHEM, V281, P934, DOI 10.1074/jbc.M506519200
  36. Mandard S, 2006, J BIOL CHEM, V281, P21575
  37. Marin JM, 2005, LANCET, V365, P1046, DOI 10.1016/S0140-6736(05)74229-X
  38. NILSSONEHLE P, 1976, J LIPID RES, V17, P536
  39. Noh HL, 2006, AM J PHYSIOL-ENDOC M, V291, pE755, DOI 10.1152/ajpendo.00111.2006
  40. Noh HL, 2007, AM J PHYSIOL-ENDOC M, V292, pE367, DOI 10.1152/ajpendo.zhl-4769-corr.2007
  41. Olivecrona T, 2009, CELLULAR LIPID METABOLISM, P315, DOI 10.1007/978-3-642-00300-4_13
  42. PAIGEN B, 1985, ATHEROSCLEROSIS, V57, P65, DOI 10.1016/0021-9150(85)90138-8
  43. Peppard PE, 2000, NEW ENGL J MED, V342, P1378, DOI 10.1056/NEJM200005113421901
  44. Punjabi NM, 2009, PLOS MED, V6, DOI 10.1371/journal.pmed.1000132
  45. Punjabi NM, 2002, AM J RESP CRIT CARE, V165, P677, DOI 10.1164/rccm.2104087
  46. Ranganathan G, 2002, J BIOL CHEM, V277, P43281, DOI 10.1074/jbc.M202560200
  47. RAYNOLDS MV, 1990, MOL ENDOCRINOL, V4, P1416
  48. Redlich CA, 1996, AM J RESP CRIT CARE, V154, P1436
  49. Sadler JE, 1997, THROMB HAEMOSTASIS, V78, P392
  50. Savransky V, 2007, AM J RESP CRIT CARE, V175, P1290, DOI 10.1164/rccm.200612-1771OC
  51. Savransky V, 2008, CIRC RES, V103, P1173, DOI 10.1161/CIRCRESAHA.108.178533
  52. Schoonjans K, 1996, EMBO J, V15, P5336
  53. Sposito AC, 2004, ATHEROSCLEROSIS, V176, P397, DOI 10.1016/j.atherosclerosis.2004.05.023
  54. Sukonina V, 2006, P NATL ACAD SCI USA, V103, P17450, DOI 10.1073/pnas.0604026103
  55. Tan KCB, 2006, ATHEROSCLEROSIS, V184, P377, DOI 10.1016/j.atheroselerosis.2005.04.024
  56. TOKUYAMA K, 1987, AM J PHYSIOL, V252, pE202
  57. Wang B, 2007, PFLUG ARCH EUR J PHY, V455, P479, DOI 10.1007/s00424-007-0301-8
  58. Wang H, 2009, AM J PHYSIOL-ENDOC M, V297, pE271, DOI 10.1152/ajpendo.90920.2008
  59. Weinstein MM, 2008, J BIOL CHEM, V283, P34511, DOI 10.1074/jbc.M806067200
  60. Weinstein MM, 2010, ARTERIOSCL THROM VAS, V30, P20, DOI 10.1161/ATVBAHA.109.196329
  61. Xu J, 2009, FREE RADICAL BIO MED, V46, P783, DOI 10.1016/j.freeradbiomed.2008.11.026
  62. Ye JP, 2007, AM J PHYSIOL-ENDOC M, V293, pE1118, DOI 10.1152/ajpendo.00435.2007
  63. Yokoe T, 2008, J PHYSIOL-LONDON, V586, P899, DOI 10.1113/jphysiol.2007.143586
  64. Yoshida K, 2002, J LIPID RES, V43, P1770, DOI 10.1194/jlr.C200010-JLR200
  65. Zhang C, 2006, J LIPID RES, V47, P2055, DOI 10.1194/jlrM600226-JLR200
  66. ZHANG SH, 1994, J CLIN INVEST, V94, P937, DOI 10.1172/JCI117460
  67. Zheng CY, 2010, CIRCULATION, V121, P1722, DOI 10.1161/CIRCULATIONAHA.109.875807
  68. [Anonymous], 2002, CIRCULATION, V106, P3143