Hypoxia induces dysregulation of lipid metabolism in HepG2 cells via activation of HIF-2α

Cellular Physiology and Biochemistry

Volumn 34, Issue 5, 2014, Pages 1427-1441

  Cao, Risheng ^a   Zhao, Xiaodan ^a,b   Li, Shuo ^a   Zhou, Haiyun ^a   Chen, Weixu ^a   Ren, Lihua ^a   Zhou, Xiqiao ^a   Zhang, Hongjie ^a   Shi, Ruihua ^a  

^a NANJING MEDICAL UNIVERSITY   (China)

^b SUZHOU MUNICIPAL HOSPITAL   (China)

Author keywords

Cholesterol metabolism; Fatty acid metabolism; HepG2; HIF 2

Indexed keywords

CHOLESTEROL; FATTY ACID; HYPOXIA INDUCIBLE FACTOR 2ALPHA; SMALL INTERFERING RNA; TRIACYLGLYCEROL; BASIC HELIX LOOP HELIX TRANSCRIPTION FACTOR; ENDOTHELIAL PAS DOMAIN-CONTAINING PROTEIN 1; MESSENGER RNA; OXYGEN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CATABOLISM; CELL HYPOXIA; CHOLESTEROL BLOOD LEVEL; CHOLESTEROL TRANSPORT; CONTROLLED STUDY; ENZYME ACTIVITY; FATTY ACID BLOOD LEVEL; FATTY ACID TRANSPORT; GENE EXPRESSION; HEPG2 CELL LINE; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; LIPID DEGRADATION; LIPID METABOLISM; LIPID STORAGE; MALE; MOUSE; NONHUMAN; PROTEIN EXPRESSION; REAL TIME POLYMERASE CHAIN REACTION; STABLE TRANSFECTION; TRANSIENT TRANSFECTION; TRIACYLGLYCEROL BLOOD LEVEL; ANIMAL; ANOXIA; C57BL MOUSE; GENETICS; HOMEOSTASIS; LIVER; METABOLISM; OXIDATION REDUCTION REACTION; PATHOLOGY; PHYSIOLOGY; SIGNAL TRANSDUCTION; TUMOR CELL LINE;

MUS;

ANIMALS; ANOXIA; BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS; CELL LINE, TUMOR; HEP G2 CELLS; HOMEOSTASIS; HUMANS; LIPID METABOLISM; LIVER; MALE; MICE; MICE, INBRED C57BL; OXIDATION-REDUCTION; OXYGEN; RNA, MESSENGER; SIGNAL TRANSDUCTION;

EID: 84908271262     PISSN: 10158987     EISSN: 14219778     Source Type: Journal    
DOI: 10.1159/000366348     Document Type: Article

References (51)

1. Byrne CD: Hypoxia and non-alcoholic fatty liver disease. Clin Sci (Lond) 2010;118:397-400.
2. Semenza GL: Oxygen sensing, hypoxia-inducible factors, and disease pathophysiology. Annu Rev Pathol 2014;9:47-71.
3. Higuchi N, Kato M, Shundo Y, Tajiri H, Tanaka M, Yamashita N, Kohjima M, Kotoh K, Nakamuta M, Takayanagi R, Enjoji M: Liver X receptor in cooperation with SREBP-lc is a major lipid synthesis regulator in nonalcoholic fatty liver disease. Hepatol Res 2008;38:1122-1129.
4. Magana MM, Koo SH, Towle HC, Osborne TF: Different sterol regulatory element-binding protein-1 isoforms utilize distinct co-regulatory factors to activate the promoter for fatty acid synthase. J Biol Chem 2000;275:4726-4733.
5. Nguyen P, Leray V, Diez M, Serisier S, Le Bloc'h J, Siliart B, Dumon H: Liver lipid metabolism. J Anim Physiol Anim Nutr (Berl) 2008;92:272-283.
6. Bengoechea-Alonso MT, Ericsson J: SREBP in signal transduction: cholesterol metabolism and beyond. Curr Opin Cell Biol 2007;19:215-222.
7. Horton JD, Goldstein JL, Brown MS: SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest 2002;109:1125-1131.
8. Burg JS, Espenshade PJ: Regulation of HMG-CoA reductase in mammals and yeast. Prog Lipid Res 2011;50:403-410.
9. Jo Y, Debose-Boyd RA: Control of cholesterol synthesis through regulated ER-associated degradation of HMG CoA reductase. Crit Rev Biochem Mol Biol 2010;45:185-198.
10. Yang SY, He XY, Schulz H: 3-Hydroxyacyl-CoA dehydrogenase and short chain 3-hydroxyacyl-CoA dehydrogenase in human health and disease. FEBS J 2005;272:4874-4883.
11. Gilardi F, Mitro N, Godio C, Scotti E, Caruso D, Crestani M, De Fabiani E: The pharmacological exploitation of cholesterol 7alpha-hydroxylase, the key enzyme in bile acid synthesis: from binding resins to chromatin remodelling to reduce plasma cholesterol. Pharmacol Ther 2007;116:449-472.
12. Gupta S, Stravitz RT, Dent P, Hylemon PB: Down-regulation of cholesterol 7alpha-hydroxylase (CYP7A1] gene expression by bile acids in primary rat hepatocytes is mediated by the c-Jun. N-terminal kinase pathway. J Biol Chem 2001;276:15816-15822.
13. Noshiro M, Usui E, Kawamoto T, Kubo H, Fujimoto K, Furukawa M, Honma S, Makishima M, Honma K, Kato Y: Multiple mechanisms regulate circadian expression of the gene for cholesterol 7alp ha-hydroxylase (Cyp7a), a key enzyme in hepatic bile acid biosynthesis. J Biol Rhythms 2007;22:299-311.
14. Field FJ, Watt K, Mathur SN: Origins of intestinal ABCAl-mediated HDL-cholesterol. J Lipid Res 2008;49:2605-2619.
15. Wang N, Tall AR: Regulation and mechanisms of ATP-binding cassette transporter Al-mediated cellular cholesterol efflux. Arterioscler Thromb Vasc Biol 2003;23:1178-1184.
16. Dikkers A, Freak de Boer J, Annema W, Groen AK, Tietge UJ: Scavenger receptor BI and ABCG5/G8 differentially impact biliary sterol secretion and reverse cholesterol transport in mice. Hepatology 2013;58:293-303.
17. Kidambi S, Patel SB: Cholesterol and non-cholesterol sterol transporters: ABCG5, ABCG8 and NPC1L1: a review. Xenobiotica 2008;38:1119-1139.
18. Majmundar AJ, Wong WJ, Simon MC: Hypoxia-inducible factors and the response to hypoxic stress. Mol Cell 2010;40:294-309.
19. Patel SA, Simon MC: Biology of hypoxia-inducible factor-2alpha in development and disease. Cell Death Differ 2008;15:628-634.
20. Tian H, McKnight SL, Russell DW: Endothelial PAS domain protein 1(EPAS1), a transcription factor selectively expressed in endothelial cells. Genes Dev 1997;11:72-82.
21. Narravula S, Colgan SP: Hypoxia-inducible factor 1-mediated inhibition of peroxisome proliferatoractivated receptor alpha expression during hypoxia. J Immunol 2001;166:7543-7548.
22. Gimm T, Wiese M, Teschemacher B, Deggerich A, Schodel J, Knaup KX, Hackenbeck T, Hellerbrand C, Amann K, Wiesener MS, Honing S, Eckardt KU, Warnecke C: Hypoxia-inducible protein 2 is a novel lipid droplet protein and a specific target gene of hypoxia-inducible factor-1. FASEB J 2010;24:4443-4458.
23. Nishiyama Y, Goda N, Kanai M, Niwa D, Osanai K, Yamamoto Y, Senoo-Matsuda N, Johnson RS, Miura S, Kabe Y, Suematsu M: HIF-lalpha induction suppresses excessive lipid accumulation in alcoholic fatty liver in mice. J Hepatol 2012;56:441-447.
24. Rankin EB, Rha J, Selak MA, Unger TL, Keith B, Liu Q, Haase VH: Hypoxia-inducible factor 2 regulates hepatic lipid metabolism. Mol Cell Biol 2009;29:4527-4538.
25. Minamishima YA, Moslehi J, Padera RF, Bronson RT, Liao R, Kaelin WG Jr: A feedback loop involving the Phd3 prolyl hydroxylase tunes the mammalian hypoxic response in vivo. Mol Cell Biol 2009;29:5729-5741.
26. Scortegagna M, Ding K, Oktay Y, Gaur A, Thurmond F, Yan LJ, Marck BT, Matsumoto AM, Shelton JM, Richardson JA, Bennett MJ, Garcia JA: Multiple organ pathology, metabolic abnormalities and impaired homeostasis of reactive oxygen species in Epasl-/-mice. Nat Genet 2003;35:331-340.
27. Kim WY, Safran M, Buckley MR, Ebert BL, Glickman J, Bosenberg M, Regan M, Kaelin WG Jr: Failure to prolyl hydroxylate hypoxia-inducible factor alpha phenocopies VHL inactivation in vivo. EMBO J 2006;25:4650-4662.
28. Abe Y, Hines IN, Zibari G, Pavlick K, Gray L, Kitagawa Y, Grisham MB: Mouse model of liver ischemia and reperfusion injury: method for studying reactive oxygen and nitrogen metabolites in vivo. Free Radic Biol Med 2009;46:1-7.
29. Ito M, Jaswal JS, Lam VH, Oka T, Zhang L, Beker DL, Lopaschuk GD, Rebeyka IM: High levels of fatty acids increase contractile function of neonatal rabbit hearts during reperfusion following ischemia. Am J Physiol Heart Circ Physiol 2010;298:H1426-1437.
30. Shrivastav S, Zhang L, Okamoto K, Lee H, Lagranha C, Abe Y, Balasubramanyam A, Lopaschuk GD, Kino T, Kopp JB: HIV-1 Vpr enhances PPARbeta/delta-mediated transcription, increases PDK4 expression, and reduces PDC activity. Mol Endocrinol 2013;27:1564-1576.
31. Rohrl C, Eigner K, Winter K, Korbelius M, Obrowsky S, Kratky D, Kovacs WJ, Stangl H: Endoplasmic reticulum stress impairs cholesterol efflux and synthesis in hepatic cells. J Lipid Res 2014;55:94-103.
32. Greenspan P, Mayer EP, Fowler SD: Nile red: a selective fluorescent stain for intracellular lipid droplets. J Cell Biol 1985;100:965-973.
33. Coughlin SR, Mawdsley L, Mugarza JA, Calverley PM, Wilding JP: Obstructive sleep apnoea is independently associated with an increased prevalence of metabolic syndrome. Eur Heart J 2004;25:735-741.
34. Drager LF, Bortolotto LA, Maki-Nunes C, Trombetta IC, Alves MJ, Fraga RF, Negrao CE, Krieger EM, Lorenzi-Filho G: The incremental role of obstructive sleep apnoea on markers of atherosclerosis in patients with metabolic syndrome. Atherosclerosis 2010;208:490-495.
35. Roche F, Sforza E, PichotV, Maudoux D, Garcin A, Celle S, Picard-Kossovsky M, Gaspoz JM, Barthelemy JC, Group PS: Obstructive sleep apnoea/hypopnea influences high-density lipoprotein cholesterol in the elderly. Sleep Med 2009;10:882-886.
36. Tan KC, Chow WS, Lam JC, Lam B, Wong WK, Tam S, Ip MS: HDL dysfunction in obstructive sleep apnea. Atherosclerosis 2006;184:377-382.
37. Tokuda F, Sando Y, Matsui H, Koike H, Yokoyama T: Serum levels of adipocytokines, adiponectin and leptin, inpatients with obstructive sleep apnea syndrome. Intern Med 2008;47:1843-1849.
38. Wiesener MS, Jurgensen JS, Rosenberger C, Scholze CK, Horstrup JH, Warnecke C, Mandriota S, Bechmann I, Frei UA, Pugh CW, Ratcliffe PJ, Bachmann S, Maxwell PH, Eckardt KU: Widespread hypoxia-inducible expression of HIF-2alpha in distinct cell populations of different organs. FASEB J 2003;17:271-273.
39. Wiesener MS, Turley H, Allen WE, Willam C, Eckardt KU, Talks KL, Wood SM, Gatter KC, Harris AL, Pugh CW, Ratcliffe PJ, Maxwell PH: Induction of endothelial PAS domain protein-1 by hypoxia: characterization and comparison with hypoxia-inducible factor-lalpha. Blood 1998;92:2260-2268.
40. Wada T, Shimba S, Tezuka M: Transcriptional regulation of the hypoxia inducible factor-2alpha (HIF-2alpha) gene during adipose differentiation in 3T3-L1 cells. Biol Pharm Bull 2006;29:49-54.
41. Hu CJ, Wang LY, Chodosh LA, Keith B, Simon MC: Differential roles of hypoxia-inducible factor lalpha (HIF-lalpha) and HIF-2alpha in hypoxic gene regulation. Mol Cell Biol 2003;23:9361-9374.
42. Guillet-Deniau I, Pichard AL, Kone A, Esnous C, Nieruchalski M, Girard J, Prip-Buus C: Glucose induces de novo lipogenesis in rat muscle satellite cells through a sterol-regulatory-element-binding-protein-1cdependent pathway. J Cell Sci 2004;117:1937-1944.
43. Shimomura I, BashmakovY, Horton JD: Increased levels of nuclear SREBP-lc associated with fatty livers in two mouse models of diabetes mellitus. J Biol Chem 1999;274:30028-30032.
44. Li J, Grigoryev DN, Ye SQ, Thorne L, Schwartz AR, Smith PL, O'Donnell CP, Polotsky VY: Chronic intermittent hypoxia upregulates genes of lipid biosynthesis in obese mice. J Appl Physiol (1985) 2005;99:1643-1648.
45. Li J, Thorne LN, Punjabi NM, Sun CK, Schwartz AR, Smith PL, Marino RL, Rodriguez A, Hubbard WC, ODonnell CP, Polotsky VY: Intermittent hypoxia induces hyperlipidemia in lean mice. Circ Res 2005;97:698-706.
46. Parathath S, Mick SL, Feig JE, Joaquin V, Grauer L, Habiel DM, Gassmann M, Gardner LB, Fisher EA: Hypoxia is present in murine atherosclerotic plaques and has multiple adverse effects on macrophage lipid metabolism. Circ Res 2011;109:1141-1152.
47. Manalo DJ, Rowan A, Lavoie T, Natarajan L, Kelly BD, Ye SQ, Garcia JG, Semenza GL: Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1. Blood 2005;105:659-669.
48. Cao R, Hu Y, Wang Y, Gurley EC, Studer EJ, Wang X, Hylemon PB, Pandak WM, Sanyal AJ, Zhang L, Zhou H: Prevention of HIV protease inhibitor-induced dysregulation of hepatic lipid metabolism by raltegravir via endoplasmic reticulum stress signaling pathways. J Pharmacol Exp Ther 2010;334:530-539.
49. Colgan SM, Hashimi AA, Austin RC: Endoplasmic reticulum stress and lipid dysregulation. Expert Rev Mol Med 2011;13:e4.
50. Lee AH, Glimcher LH: Intersection of the unfolded protein response and hepatic lipid metabolism. Cell Mol Life Sci 2009;66:2835-2850.
51. Zheng Z, Zhang C, Zhang K: Role of unfolded protein response in lipogenesis. World J Hepatol 2010;2:203-207.