title: Neuroinflammation in overnutrition-induced diseases.
abstract: Inflammation is a biological response mounted by the immune system against dangerous assaults that threaten the integrity and normal physiology of an organism. During the past decades, cross-disciplinary research from immunology and endocrinology has much broadened this knowledge by demonstrating that chronic conditions of nutritional excess constitute an independent category of inflammatory activators, and the resulting chronic and low-grade inflammation is an important characteristic of overnutrition-induced diseases. A large body of research has demonstrated that these diseases are pathogenically associated with the local, negative actions of inflammation in peripheral tissues predominantly including the liver, muscle, and fat. In this research background, more recent research has advanced to a new level, with the important discoveries showing that overnutrition-induced inflammation occurs in the brain and thus plays a broad and leadership role in overnutrition-induced diseases. While much more research establishments are expected in this emerging and quickly expanding research, the appreciated understandings have been mainly based on proinflammatory IKKβ/NF-κB pathway and related molecules in the hypothalamus. In this chapter, the author focuses on describing IKKβ/NF-κB-induced neural inflammation in the context of overnutrition-induced metabolic inflammation and especially the central roles of this neural inflammation in the development of a spectrum of overnutrition-related diseases.
authors: Department of Molecular Pharmacology, Institute of Aging, Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York, USA. dongsheng.cai@einstein.yu.edu
authors: Dongsheng
authors: D
authors: Cai
mesh_terms: D000818:Animals; D002493:Central Nervous System Diseases / Q000473:pathology*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D044343:Overnutrition / Q000150:complications* / Q000378:metabolism / Q000473:pathology
chemical_list: D016328:NF-kappa B; D051550:I-kappa B Kinase
references: Annu Rev Physiol. 2008;70:513-35
references: 17988209
references: Cell Metab. 2007 Nov;6(5):386-97
references: 17983584
references: Genes Dev. 2010 Feb 1;24(3):256-64
references: 20080940
references: Br J Pharmacol. 2012 Dec;167(7):1520-32
references: 22817481
references: Trends Pharmacol Sci. 2009 Apr;30(4):174-81
references: 19269697
references: J Clin Invest. 2011 Jun;121(6):2111-7
references: 21633179
references: Lancet Neurol. 2007 Apr;6(4):352-61
references: 17362839
references: Can J Physiol Pharmacol. 2002 Apr;80(4):258-63
references: 12025958
references: J Comp Neurol. 2005 Dec 5;493(1):63-71
references: 16254991
references: Behav Brain Funct. 2010 Jul 09;6:43
references: 20618938
references: Nat Med. 2009 Aug;15(8):930-9
references: 19633656
references: Curr Hypertens Rep. 2002 Apr;4(2):119-25
references: 11884267
references: Hypertension. 2005 Jan;45(1):9-14
references: 15583075
references: Nature. 2012 Jan 18;481(7381):278-86
references: 22258606
references: Science. 2003 Oct 31;302(5646):819-22
references: 14593166
references: J Immunol. 2009 Jul 15;183(2):1480-7
references: 19561103
references: Nat Rev Neurosci. 2005 Oct;6(10):775-86
references: 16163382
references: Nature. 2008 Jul 24;454(7203):455-62
references: 18650916
references: J Biol Chem. 2002 Jun 7;277(23):20336-42
references: 11916965
references: Cell Metab. 2009 Jan 7;9(1):35-51
references: 19117545
references: Expert Opin Investig Drugs. 2005 Apr;14(4):393-409
references: 15882116
references: Cell. 2010 Mar 19;140(6):900-17
references: 20303879
references: J Clin Invest. 2007 Jun;117(6):1670-8
references: 17525801
references: Proc Natl Acad Sci U S A. 2010 Mar 30;107(13):6028-33
references: 20231445
references: Cell Cycle. 2009 Aug 15;8(16):2542-8
references: 19633416
references: J Alzheimers Dis. 2011;24 Suppl 2:95-109
references: 21403387
references: Am J Physiol Endocrinol Metab. 2010 Jul;299(1):E47-53
references: 20371733
references: Blood. 1993 Aug 15;82(4):1212-20
references: 8353285
references: Nat Med. 2005 Dec;11(12):1322-9
references: 16286924
references: Nature. 2006 Dec 14;444(7121):854-9
references: 17167473
references: Nat Neurosci. 2005 May;8(5):579-84
references: 15856066
references: Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14875-80
references: 20679202
references: Cell. 2010 Mar 19;140(6):805-20
references: 20303872
references: Cell. 2010 Mar 19;140(6):918-34
references: 20303880
references: Nature. 2004 Jul 8;430(6996):257-63
references: 15241424
references: Science. 2008 Dec 5;322(5907):1539-43
references: 19056984
references: Biochem Biophys Res Commun. 2008 Feb 29;367(1):103-8
references: 18164680
references: Neuroendocrinology. 2008;88(3):227-34
references: 18382067
references: Annu Rev Immunol. 2011;29:415-45
references: 21219177
references: J Clin Invest. 2008 Sep;118(9):2992-3002
references: 18769626
references: Mol Neurobiol. 2002 Oct-Dec;26(2-3):283-98
references: 12428761
references: Science. 2006 Aug 25;313(5790):1137-40
references: 16931765
references: Proc Natl Acad Sci U S A. 2010 May 4;107(18):8416-21
references: 20404154
references: J Clin Invest. 2012 Jan;122(1):153-62
references: 22201683
references: Nat Med. 2004 Feb;10(2):126-7
references: 14760416
references: Annu Rev Neurosci. 2008;31:91-123
references: 18333761
references: Peptides. 2007 May;28(5):1050-8
references: 17459524
references: Nat Med. 2002 Dec;8(12):1376-82
references: 12426561
references: Nat Med. 2011 Jul 07;17(7):796-808
references: 21738161
references: Diabetes. 2007 Aug;56(8):1986-98
references: 17519423
references: Nat Med. 2004 Jul;10(7):734-8
references: 15220914
references: Neuropharmacology. 2012 Feb;62(2):890-900
references: 21964436
references: Nat Cell Biol. 2011 Mar;13(3):184-90
references: 21364565
references: Oncogene. 1999 Nov 22;18(49):6853-66
references: 10602461
references: Annu Rev Physiol. 2008;70:537-56
references: 17937601
references: J Biol Chem. 2009 Jul 3;284(27):18368-76
references: 19433583
references: J Neurochem. 2012 Feb;120(4):477-94
references: 22118687
references: Nat Neurosci. 2005 May;8(5):571-8
references: 15856065
references: Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):2939-44
references: 21282643
references: Nat Med. 2009 Aug;15(8):914-20
references: 19633658
references: J Neuroendocrinol. 2011 Apr;23(4):365-70
references: 21314736
references: J Clin Invest. 2006 Nov;116(11):3015-25
references: 17053832
references: Lancet. 2008 May 10;371(9624):1612-23
references: 18468545
references: Mol Cell Biol. 2006 Apr;26(8):3071-84
references: 16581782
references: J Neurosci. 2009 Jan 14;29(2):359-70
references: 19144836
references: Aging (Albany NY). 2012 Feb;4(2):98-115
references: 22328600
references: J Clin Invest. 2003 Dec;112(12):1821-30
references: 14679177
references: Cell. 1996 Oct 4;87(1):13-20
references: 8858144
references: Ann N Y Acad Sci. 2011 Dec;1243:E1-39
references: 22417140
references: Nat Med. 2009 Apr;15(4):373-4
references: 19350009
references: Aging Cell. 2010 Apr;9(2):135-46
references: 20041858
references: Neurobiol Dis. 2011 Jul;43(1):9-16
references: 20696248
references: Nature. 2006 Jun 15;441(7095):880-4
references: 16625205
references: J Neurosci. 2007 Nov 21;27(47):12924-32
references: 18032666
references: Science. 2006 May 12;312(5775):861-4
references: 16690851
references: Nat Cell Biol. 2012 Oct;14(10):999-1012
references: 22940906
references: Curr Opin Nephrol Hypertens. 2006 Mar;15(2):152-8
references: 16481882
references: J Clin Invest. 2005 Oct;115(10):2656-64
references: 16200199
references: J Clin Invest. 2006 Jul;116(7):1767-75
references: 16823474
references: Nat Immunol. 2002 Mar;3(3):221-7
references: 11875461
references: Curr Cardiol Rep. 2008 Nov;10(6):464-9
references: 18950555
references: J Neurochem. 2011 Feb;116(4):564-76
references: 21143598
references: Biochim Biophys Acta. 2008 Jul;1783(7):1418-35
references: 18284922
references: Cardiovasc Res. 2009 Jun 1;82(3):503-12
references: 19246475
references: Nat Med. 2004 Jul;10(7):739-43
references: 15208705
references: J Biol Chem. 2011 Sep 16;286(37):32324-32
references: 21784844
references: BMC Neurosci. 2006 Dec 01;7:78
references: 17137520
references: FASEB J. 2010 Mar;24(3):731-9
references: 19841034
references: J Neurochem. 2012 Mar;120(6):1060-71
references: 22248073
references: J Immunol. 2000 Apr 15;164(8):4292-300
references: 10754328
references: Mol Cell Biol. 2010 Jan;30(1):106-15
references: 19841069
references: Nat Rev Drug Discov. 2008 Dec;7(12):1013-30
references: 19043451
references: Nature. 2006 May 25;441(7092):513-7
references: 16724068
references: Cell. 2008 Oct 3;135(1):61-73
references: 18854155
references: Ann N Y Acad Sci. 2010 Nov;1212:97-113
references: 21070248
references: J Physiol. 2007 Sep 1;583(Pt 2):437-43
references: 17584844
references: FEBS Lett. 2002 May 22;519(1-3):231-7
references: 12023051
references: Mol Cell Biol. 2004 Dec;24(23):10161-8
references: 15542827
references: Nature. 2006 Oct 19;443(7113):787-95
references: 17051205
references: Endocrinology. 2011 Apr;152(4):1314-26
references: 21266511
references: Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10873-8
references: 9380727
references: Endocrinology. 2010 Feb;151(2):671-82
references: 20022934
references: PLoS One. 2008 Sep 05;3(9):e3151
references: 18773087
references: Eur J Pharmacol. 2010 Jun 25;636(1-3):181-8
references: 20361957
references: J Clin Invest. 2012 Jan;122(1):142-52
references: 22201680
references: Hypertension. 2011 Feb;57(2):261-8
references: 21220710
references: Cell. 2006 Oct 6;127(1):59-69
references: 17018277
references: J Clin Invest. 2004 Feb;113(3):414-24
references: 14755338
references: J Endocrinol. 2008 Dec;199(3):399-406
references: 18787058
references: Front Biosci. 2007 May 01;12:2869-75
references: 17485265
references: Am J Physiol Endocrinol Metab. 2009 May;296(5):E1003-12
references: 19116375
references: Cell. 2010 Mar 19;140(6):935-50
references: 20303881
references: Nat Med. 2009 Aug;15(8):921-9
references: 19633657
references: Science. 2002 Jun 14;296(5575):1991-5
references: 12065827
references: Cell Metab. 2009 Dec;10(6):491-8
references: 19945406
references: Curr Opin Nephrol Hypertens. 2009 Mar;18(2):128-33
references: 19434050
references: Cell. 2007 Apr 20;129(2):251-62
references: 17448988
references: Mol Psychiatry. 1998 Jan;3(1):15-20
references: 9491808
references: Nature. 2000 Aug 24;406(6798):902-6
references: 10972293
references: Nat Med. 2011 Jun 05;17(7):883-7
references: 21642978
references: J Neurosci. 2009 Jul 1;29(26):8506-11
references: 19571141
references: J Clin Invest. 2006 Jul;116(7):1761-6
references: 16823473
references: Trends Endocrinol Metab. 2006 Nov;17(9):365-71
references: 17010638
references: Nature. 2006 Sep 21;443(7109):289-95
references: 16988703
references: Nature. 2002 Nov 21;420(6913):333-6
references: 12447443
references: PLoS Biol. 2011 Jul;9(7):e1001112
references: 21814490
references: Cell Metab. 2009 Oct;10(4):249-59
references: 19808018
references: J Neurol Neurosurg Psychiatry. 2005 Oct;76(10):1366-72
references: 16170078
references: Cell Metab. 2005 Jan;1(1):15-25
references: 16054041
references: Nature. 2011 Jan 13;469(7329):221-5
references: 21124315
references: Neurosci Lett. 2004 Nov 30;372(1-2):40-5
references: 15531085
references: Endocrinology. 2010 Sep;151(9):4109-15
references: 20573720
references: Brain Res. 2009 May 1;1268:174-180
references: 19285049
references: J Clin Invest. 2003 Dec;112(12):1796-808
references: 14679176
references: Cell. 2008 Feb 8;132(3):344-62
references: 18267068