title: Mouse resistin modulates adipogenesis and glucose uptake in 3T3-L1 preadipocytes through the ROR1 receptor.
abstract: Mouse resistin, a cysteine-rich protein primarily secreted from mature adipocytes, is involved in insulin resistance and type 2 diabetes. Human resistin, however, is mainly secreted by immune mononuclear cells, and it competes with lipopolysaccharide for the binding to Toll-like receptor 4, which could mediate some of the well-known proinflammatory effects of resistin in humans. In addition, resistin has been involved in the regulation of many cell differentiation and proliferation processes, suggesting that different receptors could be involved in mediating its numerous effects. Thus, a recent work identifies an isoform of Decorin (Δ Decorin) as a functional resistin receptor in adipocyte progenitors that may regulate white adipose tissue expansion. Our work shows that the mouse receptor tyrosine kinase-like orphan receptor (ROR)1 could mediate some of the described functions of resistin in 3T3-L1 adipogenesis and glucose uptake. We have demonstrated an interaction of mouse resistin with specific domains of the extracellular region of the ROR1 receptor. This interaction results in the inhibition of ROR1 phosphorylation, modulates ERK1/2 phosphorylation, and regulates suppressor of cytokine signaling 3, glucose transporter 4, and glucose transporter 1 expression. Moreover, mouse resistin modulates glucose uptake and promotes adipogenesis of 3T3-L1 cells through ROR1. In summary, our results identify mouse resistin as a potential inhibitory ligand for the receptor ROR1 and demonstrate, for the first time, that ROR1 plays an important role in adipogenesis and glucose homeostasis in 3T3-L1 cells. These data open a new line of research that could explain important questions about the resistin mechanism of action in adipogenesis and in the development of insulin resistance.
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, Department of Inorganic and Organic Chemistry and Biochemistry, Medical School/Regional Center for Biomedical Research, University of Castilla-La Mancha, 02006 Albacete, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Sánchez-Solana
authors.forename: Jorge
authors.initials: J
authors.lastname: Laborda
authors.forename: Victoriano
authors.initials: V
authors.lastname: Baladrón
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D050156:Adipogenesis; D000818:Animals; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D051379:Mice; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000378:metabolism*; D052243:Resistin / Q000378:metabolism*; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism
chemical_list: D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D052243:Resistin; C499623:Retn protein, mouse; C495678:Slc2a1 protein, mouse; C495693:Slc2a4 protein, mouse; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; C477011:Ror1 protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases; D005947:Glucose
references.citation: Regul Pept. 2009 Jan 8;152(1-3):41-7
references.pmid: 18722482
references.citation: Trends Endocrinol Metab. 2002 Jan-Feb;13(1):18-23
references.pmid: 11750858
references.citation: J Cell Biochem. 2008 Oct 1;105(2):497-502
references.pmid: 18615587
references.citation: FEBS Lett. 2002 Jun 5;520(1-3):58-62
references.pmid: 12044870
references.citation: FEBS J. 2010 Oct;277(19):3864-75
references.pmid: 20840584
references.citation: J Cell Biochem. 2006 Oct 15;99(3):824-34
references.pmid: 16721825
references.citation: Mol Endocrinol. 2007 Feb;21(2):376-87
references.pmid: 17095577
references.citation: Curr Protein Pept Sci. 2009 Feb;10(1):96-107
references.pmid: 19275676
references.citation: Front Biosci (Landmark Ed). 2009 Jan 01;14:1902-16
references.pmid: 19273172
references.citation: Trends Endocrinol Metab. 2011 Jul;22(7):259-65
references.pmid: 21497511
references.citation: Oncol Rep. 2005 Nov;14(5):1381-4
references.pmid: 16211313
references.citation: Bioorg Med Chem Lett. 2010 Oct 15;20(20):6076-81
references.pmid: 20822902
references.citation: Eur J Endocrinol. 2004 Jun;150(6):885-92
references.pmid: 15191360
references.citation: FEBS Lett. 2003 Dec 4;555(2):243-9
references.pmid: 14644422
references.citation: Cellscience. 2006 Jan 28;2(3):68-81
references.pmid: 18049717
references.citation: Mol Cell Biol. 2005 Feb;25(4):1569-75
references.pmid: 15684405
references.citation: J Biol Chem. 2002 Sep 20;277(38):35671-81
references.pmid: 12105206
references.citation: Diabetes. 2005 Nov;54(11):3161-8
references.pmid: 16249440
references.citation: Genes Cells. 1999 Jan;4(1):41-56
references.pmid: 10231392
references.citation: Cell Stem Cell. 2011 Jul 8;9(1):74-86
references.pmid: 21683670
references.citation: J Cell Mol Med. 2010 Jun;14(6B):1419-31
references.pmid: 19754671
references.citation: J Biol Chem. 2002 Nov 29;277(48):46226-32
references.pmid: 12270934
references.citation: Circ Res. 2005 Feb 4;96(2):139-40
references.pmid: 15692090
references.citation: Mol Endocrinol. 2007 Dec;21(12):3050-61
references.pmid: 17717073
references.citation: Dev Dyn. 2010 Aug;239(8):2266-77
references.pmid: 20593419
references.citation: Science. 2004 Feb 20;303(5661):1195-8
references.pmid: 14976316
references.citation: IUBMB Life. 2008 Nov;60(11):729-33
references.pmid: 18800386
references.citation: Gene. 2003 Feb 13;305(1):27-34
references.pmid: 12594039
references.citation: Biochim Biophys Acta. 2011 Jun;1813(6):1153-64
references.pmid: 21419176
references.citation: J Cell Physiol. 2001 Dec;189(3):266-74
references.pmid: 11748584
references.citation: Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):3047-52
references.pmid: 18287027
references.citation: Matrix Biol. 2009 Jan;28(1):44-52
references.pmid: 19049867
references.citation: Diabetes. 2005 Feb;54(2):402-11
references.pmid: 15677498
references.citation: Nucleic Acids Res. 1991 Jul 25;19(14):3998
references.pmid: 1861990
references.citation: J Biol Chem. 2001 Apr 6;276(14):11252-6
references.pmid: 11278254
references.citation: Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6780-5
references.pmid: 15090646
references.citation: Diabetologia. 2002 Nov;45(11):1475-83
references.pmid: 12436329
references.citation: Endocrinology. 2008 Dec;149(12):6187-97
references.pmid: 18703624
references.citation: J Biol Chem. 2009 Oct 30;284(44):30167-76
references.pmid: 19720827
references.citation: Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2007 Jun;24(3):251-5
references.pmid: 17557231
references.citation: Genes Dev. 1997 Dec 15;11(24):3286-305
references.pmid: 9407023
references.citation: Nutr Metab (Lond). 2006 Jul 19;3:28
references.pmid: 16854242
references.citation: Acta Pharmacol Sin. 2007 Feb;28(2):221-6
references.pmid: 17241525
references.citation: Am J Physiol Cell Physiol. 2009 Dec;297(6):C1466-76
references.pmid: 19828833
references.citation: Science. 2004 May 21;304(5674):1154-8
references.pmid: 15155948
references.citation: Acta Pharmacol Sin. 2004 Dec;25(12):1705-11
references.pmid: 15569419
references.citation: J Biol Chem. 2005 Apr 22;280(16):15767-72
references.pmid: 15701628
references.citation: Clin Immunol. 2009 Nov;133(2):157-70
references.pmid: 19740705
references.citation: Blood. 2006 Aug 1;108(3):965-73
references.pmid: 16601243
references.citation: Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):502-6
references.pmid: 11209052
references.citation: Biomed Pharmacother. 2009 Jun;63(5):366-74
references.pmid: 18672341
references.citation: EMBO J. 2000 Aug 1;19(15):4046-55
references.pmid: 10921885
references.citation: Chin Med J (Engl). 2006 Mar 20;119(6):496-503
references.pmid: 16584648
references.citation: J Intern Med. 2004 Apr;255(4):439-47
references.pmid: 15049878
references.citation: J Biol Chem. 1992 Dec 25;267(36):26181-90
references.pmid: 1334494
references.citation: Life Sci. 2005 Dec 5;78(3):264-70
references.pmid: 16111715
references.citation: Mol Cell Endocrinol. 2010 Mar 25;316(2):129-39
references.pmid: 19723556