title: Linking obesity with type 2 diabetes: the role of T-bet.
abstract: Obesity is a major predisposing factor for the development of type 2 diabetes (T2D) and is an escalating public health issue around the world. The transition from obesity to T2D is preceded by the induction of a state of insulin resistance, which occurs in response to genetic factors and environmental influences, such as diet. Recent advances have implicated inflammatory immune cells and cytokines as critical pathogenic mediators of insulin resistance and T2D. In particular proinflammatory T helper (Th)1 cells and M1 macrophages are recruited to adipose tissue in response to high fat diet and directly promote the development of insulin resistance. The function of these two cell types is linked by the actions of the cytokine interferon (IFN)γ and one of its major transcriptional regulators T-bet. Recent studies in animal models of T2D demonstrate that T-bet is critical for the development of insulin resistance in response to high fat diet as T-bet-deficient animals are protected from the development of insulin resistance. These data indicate that T-bet and type 1 immunity may constitute novel sites of therapeutic intervention for the treatment of insulin resistance and T2D, in obese human patients.
authors.affiliation: Immunology and Diabetes Unit, St Vincent's Institute, University of Melbourne, Fitzroy, Victoria, Australia ; Department of Medicine, St Vincent's Hospital, University of Melbourne, Fitzroy, Victoria, Australia.
authors.forename: Jibran A
authors.initials: JA
authors.lastname: Wali
authors.affiliation: Immunology and Diabetes Unit, St Vincent's Institute, University of Melbourne, Fitzroy, Victoria, Australia ; Department of Medicine, St Vincent's Hospital, University of Melbourne, Fitzroy, Victoria, Australia.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Thomas
authors.affiliation: Immunology and Diabetes Unit, St Vincent's Institute, University of Melbourne, Fitzroy, Victoria, Australia.
authors.forename: Andrew Pr
authors.initials: AP
authors.lastname: Sutherland
keywords: IFNγ; T-bet; Th1; immune system; insulin resistance; obesity; type 2 diabetes
references.citation: Nat Med. 2005 Feb;11(2):183-90
references.pmid: 15685173
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):979-84
references.pmid: 17210919
references.citation: PLoS One. 2013 Aug 27;8(8):e71108
references.pmid: 24013136
references.citation: J Exp Med. 2005 Nov 7;202(9):1289-300
references.pmid: 16275766
references.citation: Nature. 2001 Dec 13;414(6865):813-20
references.pmid: 11742414
references.citation: J Endocrinol. 1999 Aug;162(2):207-14
references.pmid: 10425458
references.citation: Nat Med. 2011 May;17(5):610-7
references.pmid: 21499269
references.citation: Nat Med. 2009 Aug;15(8):930-9
references.pmid: 19633656
references.citation: Nat Immunol. 2011 Jun 20;12(7):597-606
references.pmid: 21685955
references.citation: J Biol Chem. 2009 Nov 13;284(46):31936-44
references.pmid: 19776010
references.citation: Nat Genet. 2009 Jun;41(6):703-7
references.pmid: 19430480
references.citation: Nature. 2006 Dec 21;444(7122):1027-31
references.pmid: 17183312
references.citation: Diabetes. 2012 Jul;61(7):1680-90
references.pmid: 22474027
references.citation: Mol Cell. 2005 Apr 1;18(1):13-24
references.pmid: 15808505
references.citation: Cell. 2007 Oct 5;131(1):33-45
references.pmid: 17923086
references.citation: Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5545-50
references.pmid: 11960012
references.citation: Semin Immunol. 2012 Dec;24(6):436-42
references.pmid: 23333525
references.citation: J Biol Chem. 2005 May 20;280(20):20148-53
references.pmid: 15774472
references.citation: J Clin Invest. 2007 Jan;117(1):175-84
references.pmid: 17200717
references.citation: Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15718-23
references.pmid: 15505215
references.citation: J Clin Invest. 2008 Sep;118(9):2992-3002
references.pmid: 18769626
references.citation: Annu Rev Immunol. 2003;21:713-58
references.pmid: 12500979
references.citation: Proc Natl Acad Sci U S A. 2013 Aug 20;110(34):E3216-24
references.pmid: 23922396
references.citation: Nat Med. 2009 Aug;15(8):914-20
references.pmid: 19633658
references.citation: Science. 2003 Jun 6;300(5625):1574-7
references.pmid: 12791994
references.citation: Nat Immunol. 2011 May;12(5):408-15
references.pmid: 21478880
references.citation: Mol Aspects Med. 2012 Feb;33(1):26-34
references.pmid: 22040698
references.citation: Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15818-23
references.pmid: 14673093
references.citation: J Biol Chem. 2006 Sep 15;281(37):26865-75
references.pmid: 16798732
references.citation: Nature. 2006 Dec 21;444(7122):1022-3
references.pmid: 17183309
references.citation: Cell Metab. 2013 Apr 2;17(4):520-33
references.pmid: 23562076
references.citation: Curr Protoc Pharmacol. 2012 Sep;Chapter 5:Unit5.61
references.pmid: 22948848
references.citation: J Biol Chem. 1999 Aug 20;274(34):24202-10
references.pmid: 10446195
references.citation: J Endocrinol. 2003 Nov;179(2):253-66
references.pmid: 14596677
references.citation: Diabetes. 2002 Dec;51(12):3391-9
references.pmid: 12453891
references.citation: J Biol Chem. 2003 Mar 21;278(12):10297-303
references.pmid: 12525490
references.citation: Am J Physiol Regul Integr Comp Physiol. 2011 May;300(5):R1200-8
references.pmid: 21325642
references.citation: Diabetes. 2002 Jul;51(7):2005-11
references.pmid: 12086926
references.citation: Proc Natl Acad Sci U S A. 2005 Sep 13;102(37):13248-53
references.pmid: 16135562
references.citation: Diabetes. 2008 Dec;57(12):3239-46
references.pmid: 18829989
references.citation: Nat Med. 2011 Feb;17(2):179-88
references.pmid: 21217695
references.citation: Diabetes. 2007 Jan;56(1):16-23
references.pmid: 17192460
references.citation: Nat Rev Mol Cell Biol. 2006 Feb;7(2):85-96
references.pmid: 16493415
references.citation: Nature. 2012 Jun 28;486(7404):549-53
references.pmid: 22722857
references.citation: Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7749-54
references.pmid: 12802010
references.citation: Semin Immunol. 2011 Dec;23(6):431-7
references.pmid: 21724410
references.citation: J Clin Invest. 2004 Sep;114(6):823-7
references.pmid: 15372106
references.citation: J Clin Invest. 2000 Aug;106(4):467-72
references.pmid: 10953021
references.citation: Diabetes. 2011 Mar;60(3):797-809
references.pmid: 21266330
references.citation: Nat Immunol. 2012 Mar 19;13(4):352-7
references.pmid: 22430788
references.citation: FEBS Lett. 2009 Sep 17;583(18):3045-9
references.pmid: 19695247
references.citation: Immunity. 2012 Oct 19;37(4):674-84
references.pmid: 23063332
references.citation: J Biol Chem. 2002 Nov 1;277(44):42394-8
references.pmid: 12228220
references.citation: J Lipid Res. 2011 Feb;52(2):221-36
references.pmid: 21097823
references.citation: Nat Med. 2012 Mar 06;18(3):363-74
references.pmid: 22395709
references.citation: J Clin Invest. 2006 Jul;116(7):1793-801
references.pmid: 16823477
references.citation: Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):11070-5
references.pmid: 16033867
references.citation: J Biol Chem. 1997 Nov 21;272(47):29911-8
references.pmid: 9368067
references.citation: Immunity. 2004 Apr;20(4):477-94
references.pmid: 15084276
references.citation: J Mol Endocrinol. 2011 Jun 17;47(1):R1-10
references.pmid: 21498522
references.citation: Nat Rev Immunol. 2004 Nov;4(11):900-11
references.pmid: 15516969
references.citation: Nat Rev Immunol. 2011 Feb;11(2):98-107
references.pmid: 21233852
references.citation: Science. 2002 Jan 11;295(5553):336-8
references.pmid: 11786643
references.citation: Diabetes. 2013 Jan;62(1):194-204
references.pmid: 23086037
references.citation: Mol Cell. 2002 Aug;10(2):417-26
references.pmid: 12191486
references.citation: Cell Metab. 2007 Mar;5(3):167-79
references.pmid: 17339025
references.citation: Diabetes. 2004 Dec;53 Suppl 3:S16-21
references.pmid: 15561905
references.citation: Nat Med. 2009 Aug;15(8):921-9
references.pmid: 19633657
references.citation: Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):15324-9
references.pmid: 21876127
references.citation: Nat Immunol. 2011 Jan;12(1):96-104
references.pmid: 21151104
references.citation: J Exp Med. 2002 May 6;195(9):1129-43
references.pmid: 11994418
references.citation: Cell Metab. 2013 Jun 4;17(6):851-859
references.pmid: 23747244
references.citation: Nature. 2002 Nov 21;420(6913):333-6
references.pmid: 12447443
references.citation: Blood. 2005 Nov 15;106(10):3432-9
references.pmid: 16014561
references.citation: Ann N Y Acad Sci. 2010 Nov;1212:59-77
references.pmid: 21091714
references.citation: Metabolism. 2012 Aug;61(8):1152-61
references.pmid: 22386937
references.citation: Cell. 2000 Mar 17;100(6):655-69
references.pmid: 10761931
references.citation: Science. 2005 Jan 21;307(5708):430-3
references.pmid: 15662016
references.citation: Cell. 2012 Mar 2;148(5):852-71
references.pmid: 22385956
references.citation: J Diabetes Metab. 2012 Jun 23;3(198):
references.pmid: 23243555
references.citation: J Immunol. 2008 Jun 15;180(12):8004-10
references.pmid: 18523263
references.citation: Nat Med. 2005 Feb;11(2):191-8
references.pmid: 15685170
references.citation: Science. 2002 Jan 11;295(5553):338-42
references.pmid: 11786644
references.citation: Endocrinology. 2011 Oct;152(10):3690-9
references.pmid: 21791564
references.citation: Am J Prev Med. 2012 Jun;42(6):563-70
references.pmid: 22608371
references.citation: Nat Rev Immunol. 2013 Nov;13(11):777-89
references.pmid: 24113868
references.citation: Cell Metab. 2012 May 2;15(5):585-94
references.pmid: 22560211
references.citation: Cell Metab. 2013 Mar 5;17(3):411-22
references.pmid: 23473035
references.citation: Nature. 2013 Jun 6;498(7452):99-103
references.pmid: 23719380
references.citation: Circ Res. 2008 Aug 29;103(5):467-76
references.pmid: 18658050
references.citation: Annu Rev Immunol. 2010;28:445-89
references.pmid: 20192806