title: Hypoxia-inducible factor-2α-dependent hypoxic induction of Wnt10b expression in adipogenic cells.
abstract: Adipocyte hyperplasia and hypertrophy in obesity can lead to many changes in adipose tissue, such as hypoxia, metabolic dysregulation, and enhanced secretion of cytokines. In this study, hypoxia increased the expression of Wnt10b in both human and mouse adipogenic cells, but not in hypoxia-inducible factor (HIF)-2α-deficient adipogenic cells. Chromatin immunoprecipitation analysis revealed that HIF-2α, but not HIF-1α, bound to the Wnt10b enhancer region as well as upstream of the Wnt1 gene, which is encoded by an antisense strand of the Wnt10b gene. Hypoxia-conditioned medium (H-CM) induced phosphorylation of lipoprotein-receptor-related protein 6 as well as β-catenin-dependent gene expression in normoxic cells, which suggests that H-CM contains canonical Wnt signals. Furthermore, adipogenesis of both human mesenchymal stem cells and mouse preadipocytes was inhibited by H-CM even under normoxic conditions. These results suggest that O2 concentration gradients influence the formation of Wnt ligand gradients, which are involved in the regulation of pluripotency, cell proliferation, and cell differentiation.
authors.affiliation: From the Department of Life Science, University of Seoul, 163 Seoulsiripdae-ro, Dongdaemun-gu, Seoul 130-743, Korea.
authors.forename: Young-Kwon
authors.initials: YK
authors.lastname: Park
authors.affiliation: From the Department of Life Science, University of Seoul, 163 Seoulsiripdae-ro, Dongdaemun-gu, Seoul 130-743, Korea.
authors.forename: Bongju
authors.initials: B
authors.lastname: Park
authors.affiliation: From the Department of Life Science, University of Seoul, 163 Seoulsiripdae-ro, Dongdaemun-gu, Seoul 130-743, Korea.
authors.forename: Seongyeol
authors.initials: S
authors.lastname: Lee
authors.affiliation: From the Department of Life Science, University of Seoul, 163 Seoulsiripdae-ro, Dongdaemun-gu, Seoul 130-743, Korea.
authors.forename: Kang
authors.initials: K
authors.lastname: Choi
authors.affiliation: From the Department of Life Science, University of Seoul, 163 Seoulsiripdae-ro, Dongdaemun-gu, Seoul 130-743, Korea.
authors.forename: Yunwon
authors.initials: Y
authors.lastname: Moon
authors.affiliation: From the Department of Life Science, University of Seoul, 163 Seoulsiripdae-ro, Dongdaemun-gu, Seoul 130-743, Korea. Electronic address: hspark@uos.ac.kr.
authors.forename: Hyunsung
authors.initials: H
authors.lastname: Park
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology; D049109:Cell Proliferation; D004742:Enhancer Elements, Genetic / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D060488:Low Density Lipoprotein Receptor-Related Protein-6 / Q000235:genetics / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D010100:Oxygen / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D051153:Wnt Proteins / Q000096:biosynthesis* / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000502:physiology; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D010100:Oxygen; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D000099162:Endothelial PAS Domain-Containing Protein 1; C497442:HIF1A protein, human; C497443:Hif1a protein, mouse; C491119:WNT10B protein, human; C102068:Wnt10b protein, mouse
keywords: Adipogenesis; HIF-2α; Hypoxia; Hypoxia-inducible Factor; Hypoxia-inducible Factor (HIF); Wnt Signaling; Wnt1; Wnt10b
references.citation: J Biol Chem. 2002 Oct 11;277(41):38239-44
references.pmid: 12154096
references.citation: Dev Cell. 2009 Jul;17(1):9-26
references.pmid: 19619488
references.citation: Diabetes. 2009 Jul;58(7):1550-7
references.pmid: 19351711
references.citation: Reproduction. 2010 Jan;139(1):85-97
references.pmid: 19755485
references.citation: J Clin Invest. 2011 Jun;121(6):2094-101
references.pmid: 21633177
references.citation: Oncogene. 1997 Oct;15(18):2133-44
references.pmid: 9393971
references.citation: Diabetes. 2007 Feb;56(2):295-303
references.pmid: 17259372
references.citation: J Biol Chem. 2010 Jan 29;285(5):3289-99
references.pmid: 19940121
references.citation: Physiol Rev. 2013 Jan;93(1):1-21
references.pmid: 23303904
references.citation: Development. 2009 Oct;136(19):3205-14
references.pmid: 19736321
references.citation: Diabetes. 2007 Apr;56(4):901-11
references.pmid: 17395738
references.citation: Nat Cell Biol. 2010 Oct;12(10):1007-13
references.pmid: 20852629
references.citation: Genes Dev. 2006 Mar 1;20(5):557-70
references.pmid: 16510872
references.citation: Nat Cell Biol. 2003 Aug;5(8):741-7
references.pmid: 12855956
references.citation: Oncogene. 2012 May 3;31(18):2283-97
references.pmid: 21927022
references.citation: Science. 2000 Aug 11;289(5481):950-3
references.pmid: 10937998
references.citation: EMBO J. 1998 Jun 1;17(11):3005-15
references.pmid: 9606183
references.citation: Am J Physiol Endocrinol Metab. 2007 Oct;293(4):E1118-28
references.pmid: 17666485
references.citation: J Biol Chem. 2001 Mar 16;276(11):7919-26
references.pmid: 11112789
references.citation: Cell Stem Cell. 2010 Aug 6;7(2):150-61
references.pmid: 20682444
references.citation: Nat Rev Cancer. 2011 Dec 15;12(1):9-22
references.pmid: 22169972
references.citation: Int J Obes (Lond). 2011 Nov;35(11):1450-4
references.pmid: 21285942
references.citation: Mol Cell Biol. 2003 Jan;23(1):359-69
references.pmid: 12482987
references.citation: Cell. 2012 Feb 3;148(3):399-408
references.pmid: 22304911
references.citation: Genes Dev. 1998 Nov 1;12(21):3320-4
references.pmid: 9808618
references.citation: J Biol Chem. 2009 Jun 19;284(25):16767-16775
references.pmid: 19386601
references.citation: Genes Dev. 2010 Mar 1;24(5):491-501
references.pmid: 20194441
references.citation: Nat Cell Biol. 2007 Feb;9(2):210-7
references.pmid: 17220880
references.citation: Diabetes. 2009 Jan;58(1):95-103
references.pmid: 18984735
references.citation: Mol Cell Biol. 2009 Aug;29(16):4467-83
references.pmid: 19546236
references.citation: Bone. 2012 Feb;50(2):477-89
references.pmid: 21872687
references.citation: Nat Cell Biol. 2007 Nov;9(11):1273-85
references.pmid: 17952062
references.citation: EMBO J. 2012 Jun 13;31(12):2705-13
references.pmid: 22617425
references.citation: Cell. 2012 Jun 8;149(6):1192-205
references.pmid: 22682243
references.citation: J Biol Chem. 2010 Apr 30;285(18):14031-41
references.pmid: 20179324
references.citation: Mol Cell Biol. 2003 Dec;23(24):9361-74
references.pmid: 14645546
references.citation: Blood. 2011 Jun 9;117(23):e207-17
references.pmid: 21447827
references.citation: Nat Chem Biol. 2009 Feb;5(2):100-7
references.pmid: 19125156
references.citation: J Cell Sci. 2006 Jun 15;119(Pt 12):2613-2620
references.pmid: 16763196
references.citation: Cancer Cell. 2006 Nov;10(5):413-23
references.pmid: 17097563
references.citation: Methods. 2001 Dec;25(4):386-401
references.pmid: 11846608
references.citation: J Biol Chem. 2002 Aug 23;277(34):30998-1004
references.pmid: 12055200
references.citation: Cell Stem Cell. 2011 Oct 4;9(4):298-310
references.pmid: 21982230
references.citation: J Biol Chem. 2008 Dec 12;283(50):35096-105
references.pmid: 18957421
references.citation: J Cell Sci. 2008 Mar 15;121(Pt 6):737-46
references.pmid: 18322270