title: The role of adiponectin signaling in metabolic syndrome and cancer.
abstract: The increased prevalence of obesity has mandated extensive research focused on mechanisms responsible for associated clinical complications. Emerging from the focus on adipose tissue biology as a vitally important adipokine is adiponectin which is now believed to mediate anti-diabetic, anti-atherosclerotic, anti-inflammatory, cardioprotective and cancer modifying actions. Adiponectin mediates these primarily beneficial effects via direct signaling effects and via enhancing insulin sensitivity via crosstalk with insulin signaling pathways. Reduced adiponectin action is detrimental and occurs in obesity via decreased circulating levels of adiponectin action or development of adiponectin resistance. This review will focus on cellular mechanisms of adiponectin action, their crosstalk with insulin signaling and the resultant role of adiponectin in cardiovascular disease, diabetes and cancer and reviews data from in vitro cell based studies through animal models to clinical observations.
authors.affiliation: Department of Biology, York University, Toronto, ON, M3J 1P3, Canada.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Scheid
authors.forename: Gary
authors.initials: G
authors.lastname: Sweeney
mesh_terms: D052242:Adiponectin / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D006801:Humans; D024821:Metabolic Syndrome / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D052242:Adiponectin
references.citation: Mol Endocrinol. 2011 Oct;25(10):1773-85
references.pmid: 21835890
references.citation: Clin Cancer Res. 2003 Nov 15;9(15):5699-704
references.pmid: 14654554
references.citation: Obes Facts. 2009;2(2):117-25
references.pmid: 20054215
references.citation: Biochem Soc Trans. 2013 Apr;41(2):687-93
references.pmid: 23514177
references.citation: Cell Metab. 2013 Jan 8;17(1):113-24
references.pmid: 23274086
references.citation: Cell Metab. 2009 May;9(5):417-27
references.pmid: 19416712
references.citation: Diabetes. 2012 Jun;61(6):1463-70
references.pmid: 22415879
references.citation: J Biol Chem. 2009 Aug 14;284(33):22426-22435
references.pmid: 19520843
references.citation: Nat Med. 2005 Oct;11(10):1096-103
references.pmid: 16155579
references.citation: Am J Hypertens. 2011 Mar;24(3):270-7
references.pmid: 21151013
references.citation: J Biol. 2003;2(4):26
references.pmid: 14575531
references.citation: Curr Opin Genet Dev. 2013 Feb;23(1):53-62
references.pmid: 23317514
references.citation: Cell Metab. 2006 Jul;4(1):75-87
references.pmid: 16814734
references.citation: Nat Med. 2007 Mar;13(3):332-9
references.pmid: 17268472
references.citation: Cancer Res. 2009 May 1;69(9):4018-26
references.pmid: 19366811
references.citation: J Biol Chem. 2011 Sep 16;286(37):32790-800
references.pmid: 21784858
references.citation: Clin Pharmacol Ther. 2011 Jul;90(1):188-90
references.pmid: 21654743
references.citation: J Biol Chem. 2010 Oct 29;285(44):33623-31
references.pmid: 20709750
references.citation: Circulation. 2012 Sep 4;126(10):1301-13
references.pmid: 22949540
references.citation: J Mol Endocrinol. 2005 Dec;35(3):465-76
references.pmid: 16326833
references.citation: Ann N Y Acad Sci. 2012 Oct;1271:37-43
references.pmid: 23050962
references.citation: Nature. 2010 Apr 29;464(7293):1313-9
references.pmid: 20357764
references.citation: Genes Cells. 2003 Jan;8(1):65-79
references.pmid: 12558800
references.citation: Endocrinology. 2010 Jan;151(1):322-31
references.pmid: 19850745
references.citation: Science. 2009 Dec 18;326(5960):1707-11
references.pmid: 19892943
references.citation: EMBO J. 2003 Oct 1;22(19):5102-14
references.pmid: 14517248
references.citation: Antioxid Redox Signal. 2011 Oct 1;15(7):1779-88
references.pmid: 21091073
references.citation: Neoplasia. 2013 Jan;15(1):23-38
references.pmid: 23358729
references.citation: J Biol Chem. 2005 Apr 22;280(16):16456-60
references.pmid: 15716268
references.citation: Am J Physiol Endocrinol Metab. 2007 Dec;293(6):E1836-44
references.pmid: 17940218
references.citation: J Clin Endocrinol Metab. 2007 Mar;92(3):1041-8
references.pmid: 17192291
references.citation: Physiol Rev. 2008 Apr;88(2):389-419
references.pmid: 18391168
references.citation: FEBS Lett. 2003 Jul 3;546(1):159-65
references.pmid: 12829253
references.citation: J Cell Physiol. 2010 Jan;222(1):149-55
references.pmid: 19780028
references.citation: J Endocrinol. 2011 Jul;210(1):81-92
references.pmid: 21543456
references.citation: Nature. 2003 Jun 12;423(6941):762-9
references.pmid: 12802337
references.citation: Br J Pharmacol. 2012 Feb;165(3):574-90
references.pmid: 21457225
references.citation: BMC Biol. 2013 Apr 15;11:36
references.pmid: 23587167
references.citation: Diabetes. 2007 Mar;56(3):583-93
references.pmid: 17327425
references.citation: Nature. 2009 Apr 23;458(7241):1056-60
references.pmid: 19262508
references.citation: Diabetologia. 2012 Sep;55(9):2319-26
references.pmid: 22688349
references.citation: Cardiovasc Res. 2007 Jul 1;75(1):148-57
references.pmid: 17499232
references.citation: Clin Cancer Res. 2013 Apr 15;19(8):1926-32
references.pmid: 23355630
references.citation: Mol Cell Biol. 2009 Jul;29(13):3582-96
references.pmid: 19414597
references.citation: Arterioscler Thromb Vasc Biol. 2008 May;28(5):863-70
references.pmid: 18309113
references.citation: Biochem J. 2012 Jan 1;441(1):1-21
references.pmid: 22168436
references.citation: Oncol Rep. 2008 Mar;19(3):787-93
references.pmid: 18288417
references.citation: J Mol Cell Cardiol. 2010 Aug;49(2):210-20
references.pmid: 20206634
references.citation: Cell Metab. 2013 Feb 5;17(2):185-96
references.pmid: 23352188
references.citation: Endocr Rev. 2005 May;26(3):439-51
references.pmid: 15897298
references.citation: Lipids Health Dis. 2012 Oct 10;11:134
references.pmid: 23046739
references.citation: Cancer Cell. 2004 Jul;6(1):91-9
references.pmid: 15261145
references.citation: J Biol Chem. 2004 Jul 16;279(29):30817-22
references.pmid: 15123605
references.citation: Oncol Rep. 2009 Jun;21(6):1611-9
references.pmid: 19424644
references.citation: Proc Natl Acad Sci U S A. 2004 Jul 13;101(28):10308-13
references.pmid: 15210937
references.citation: Nutr Cancer. 2011;63(1):80-8
references.pmid: 21108124
references.citation: J Biol Chem. 2006 Sep 1;281(35):25336-43
references.pmid: 16835226
references.citation: EMBO J. 1992 Sep;11(9):3469-79
references.pmid: 1380456
references.citation: J Biol Chem. 2007 Nov 2;282(44):32280-7
references.pmid: 17848569
references.citation: J Cell Biol. 2004 Jul 19;166(2):213-23
references.pmid: 15249583
references.citation: J Biol Chem. 2002 Sep 20;277(38):34658-61
references.pmid: 12151381
references.citation: Front Endocrinol (Lausanne). 2011 Nov 08;2:62
references.pmid: 22649379
references.citation: Science. 2009 May 22;324(5930):1029-33
references.pmid: 19460998
references.citation: J Cell Sci. 2004 Dec 15;117(Pt 26):6365-75
references.pmid: 15561763
references.citation: FEBS Lett. 2003 Jul 3;546(1):108-12
references.pmid: 12829245
references.citation: Cell Metab. 2007 Jul;6(1):55-68
references.pmid: 17618856
references.citation: Endocr Rev. 2012 Aug;33(4):547-94
references.pmid: 22547160
references.citation: Cardiovasc Res. 2012 Jan 1;93(1):69-78
references.pmid: 22012952
references.citation: Med Oncol. 2007;24(4):361-6
references.pmid: 17917082
references.citation: Nat Cell Biol. 2006 May;8(5):516-23
references.pmid: 16622416
references.citation: J Biol Chem. 2002 Jul 19;277(29):25863-6
references.pmid: 12032136
references.citation: Science. 2010 Dec 3;330(6009):1340-4
references.pmid: 21127244
references.citation: Am J Physiol Endocrinol Metab. 2011 Sep;301(3):E447-55
references.pmid: 21586697
references.citation: Diabetes. 2011 Nov;60(11):3044-54
references.pmid: 21926268
references.citation: Exp Diabetes Res. 2011;2011:692536
references.pmid: 21331343
references.citation: PLoS One. 2011;6(8):e23967
references.pmid: 21912612
references.citation: Oncogene. 1999 Sep 2;18(35):4891-8
references.pmid: 10490823
references.citation: EMBO J. 2003 Jun 16;22(12):3062-72
references.pmid: 12805220
references.citation: J Biol Chem. 2010 Feb 26;285(9):6377-89
references.pmid: 20040596
references.citation: PLoS One. 2009;4(3):e4968
references.pmid: 19319191
references.citation: Carcinogenesis. 2008 Nov;29(11):2195-202
references.pmid: 18701434
references.citation: Curr Hypertens Rep. 2011 Apr;13(2):142-8
references.pmid: 21298579
references.citation: Hormones (Athens). 2012 Jan-Mar;11(1):8-20
references.pmid: 22450341
references.citation: Cancer Lett. 2007 Jun 8;250(2):229-36
references.pmid: 17123704
references.citation: Br J Cancer. 2008 Jan 29;98(2):370-9
references.pmid: 18182989
references.citation: Eur Heart J. 2008 May;29(9):1168-80
references.pmid: 18390538
references.citation: PLoS One. 2011 Apr 28;6(4):e19143
references.pmid: 21552570
references.citation: EMBO J. 2009 Mar 18;28(6):677-85
references.pmid: 19197243
references.citation: Cancer Res. 2006 Dec 1;66(23):11462-70
references.pmid: 17145894
references.citation: Am J Physiol Endocrinol Metab. 2009 Sep;297(3):E657-64
references.pmid: 19531641
references.citation: Cancer Prev Res (Phila). 2008 Jun;1(1):65-76
references.pmid: 19138937
references.citation: J Clin Oncol. 2011 Jan 1;29(1):32-9
references.pmid: 21115858
references.citation: Cell. 2003 Nov 26;115(5):577-90
references.pmid: 14651849
references.citation: J Biol Chem. 2009 Nov 13;284(46):31608-15
references.pmid: 19661063
references.citation: Cell. 2007 Jun 29;129(7):1261-74
references.pmid: 17604717
references.citation: J Mol Cell Cardiol. 2007 Jun;42(6):1065-74
references.pmid: 17499764
references.citation: Nature. 2005 Mar 3;434(7029):113-8
references.pmid: 15744310
references.citation: Nat Rev Cancer. 2011 May;11(5):325-37
references.pmid: 21508971
references.citation: Diabetes Metab Res Rev. 2007 Nov;23(8):600-11
references.pmid: 17966120
references.citation: Diabetes. 2001 May;50(5):1126-33
references.pmid: 11334417
references.citation: Nat Med. 2002 Nov;8(11):1288-95
references.pmid: 12368907
references.citation: Endocrinology. 2012 Nov;153(11):5231-46
references.pmid: 22989629
references.citation: Int J Cancer. 2001 Feb 1;91(3):421-30
references.pmid: 11169969
references.citation: Heart Fail Rev. 2013 Sep;18(5):631-44
references.pmid: 22893246
references.citation: Endocrinology. 2007 Sep;148(9):4411-9
references.pmid: 17569760
references.citation: Diabetes. 2007 May;56(5):1387-94
references.pmid: 17287464
references.citation: Nat Rev Mol Cell Biol. 2007 Oct;8(10):774-85
references.pmid: 17712357
references.citation: Cancer Lett. 2006 Jun 8;237(1):109-14
references.pmid: 16019138
references.citation: Cell Metab. 2005 Jul;2(1):9-19
references.pmid: 16054095
references.citation: J Cell Physiol. 2012 Jul;227(7):2917-26
references.pmid: 21938726
references.citation: J Biol Chem. 2007 Mar 16;282(11):7991-6
references.pmid: 17244624
references.citation: Am J Physiol Endocrinol Metab. 2010 Nov;299(5):E721-9
references.pmid: 20739511
references.citation: Nat Med. 2004 Dec;10(12):1384-9
references.pmid: 15558058
references.citation: Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):12017-22
references.pmid: 17609368
references.citation: J Biol Chem. 1996 May 3;271(18):10697-703
references.pmid: 8631877
references.citation: J Nutr. 2003 Nov;133(11 Suppl 1):3827S-3829S
references.pmid: 14608121
references.citation: Ann Med. 2008;40(7):514-23
references.pmid: 18608131
references.citation: Arq Bras Endocrinol Metabol. 2009 Mar;53(2):201-12
references.pmid: 19466213
references.citation: Oncogene. 2009 Jul 23;28(29):2621-33
references.pmid: 19483724
references.citation: Diabetologia. 2005 Jan;48(1):132-9
references.pmid: 15619075
references.citation: Circ Heart Fail. 2012 May 1;5(3):340-8
references.pmid: 22379072
references.citation: J Clin Endocrinol Metab. 2004 Mar;89(3):1102-7
references.pmid: 15001594
references.citation: J Biol Chem. 2004 Aug 20;279(34):35298-305
references.pmid: 15199052
references.citation: Neuropharmacology. 2012 Jul;63(1):57-75
references.pmid: 22200617
references.citation: Nat Med. 2002 Jul;8(7):731-7
references.pmid: 12068289
references.citation: Biochem Biophys Res Commun. 2006 Jun 23;345(1):271-9
references.pmid: 16678125
references.citation: Circulation. 2000 Sep 12;102(11):1296-301
references.pmid: 10982546
references.citation: Cardiology. 2011;118(4):236-7
references.pmid: 21720158
references.citation: Diabetologia. 2011 Aug;54(8):2122-31
references.pmid: 21562756
references.citation: Cell Metab. 2005 Jul;2(1):21-33
references.pmid: 16054096
references.citation: Am J Med Sci. 2012 Jan;343(1):13-6
references.pmid: 22205060