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Inflammation: the Common Link in Brain Pathologies pp 297–323Cite as

Obesity and Neuroinflammation

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Abstract

Obesity is the core and baseline component of metabolic syndrome and is a major risk factor for many diseases like Type II diabetes, cardiovascular diseases, hypertension, stroke and neurodegenerative diseases. Sedentary lifestyle, unhealthy eating habits and genetic predisposition are responsible for the increasing prevalence of obesity worldwide. Chronic overnutrition causes low-grade inflammation in several peripheral tissues as well as central nervous system, particularly hypothalamus. Activation of various proinflammatory pathways such as IKKβ/NF-κB, JNK and PKR are thought to be the major players in the induction of systemic and central inflammation. Further, neuroinflammation causes intracellular disturbances and exacerbates various stresses such as oxidative stress, ER stress and autophagic defects leading to impaired neurohormonal signalling as well as autonomic regulation of nutrient metabolism and energy balance. As obesity poses major health threat, effective therapies to minimize obesity-related comorbidities are surely needed. By targeting the inflammatory component, the progression of obesity can be slowed down. In vivo studies from our lab suggest that Withania somnifera helps to reduce hypothalamic inflammation triggered by high-fat-diet-induced obesity. Various lifestyle interventions along with herbal supplementation may effectively help to prevent obesity and its associated pathologies.

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References

  • Aron-Wisnewsky J, Tordjman J, Poitou C, Darakhshan F, Hugol D, Basdevant A, Aissat A, Guerre-Millo M, Clement K (2009) Human adipose tissue macrophages: m1 and m2 cell surface markers in subcutaneous and omental depots and after weight loss. J Clin Endocrinol Metab 94(11):4619–4623

    Article  CAS  PubMed  Google Scholar 

  • Atlantis E, Baker M (2008) Obesity effects on depression: systematic review of epidemiological studies. Int J Obes 32(6):881–891

    Article  CAS  Google Scholar 

  • Barkin SL (2013) The relationship between executive function and obesity in children and adolescents: a systematic literature review. J Obes

    Google Scholar 

  • Benigni A, Cassis P, Remuzzi G (2010) Angiotensin II revisited: new roles in inflammation, immunology and aging. EMBO Mol Med 2(7):247–257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bjørbæk C, Hollenberg AN (2002) Leptin and melanocortin signaling in the hypothalamus. Vitam Horm 65:281–311

    Article  PubMed  Google Scholar 

  • Blakemore AI, Froguel P (2010) Investigation of Mendelian forms of obesity holds out the prospect of personalized medicine. Ann N Y Acad Sci 1214(1):180–189

    Article  CAS  PubMed  Google Scholar 

  • Blatteis CM (2007) The onset of fever: new insights into its mechanism. Prog Brain Res 162:3–14

    Article  CAS  PubMed  Google Scholar 

  • Bogoyevitch MA, Ngoei KR, Zhao TT, Yeap YY, Ng DC (2010) c-Jun N-terminal kinase (JNK) signaling: recent advances and challenges. Biochimica et Biophysica Acta (BBA) Proteins Proteomics 1804(3):463–475

    Google Scholar 

  • Braun TP, Zhu X, Szumowski M, Scott GD, Grossberg AJ, Levasseur PR, Graham K, Khan S, Damaraju S, Colmers WF, Baracos VE (2011) Central nervous system inflammation induces muscle atrophy via activation of the hypothalamic–pituitary–adrenal axis. J Exp Med 208(12):2449–2463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bray GA, Popkin BM (1998) Dietary fat intake does affect obesity! Am J Clin Nutr 68(6):1157–1173

    Google Scholar 

  • Buckman LB, Hasty AH, Flaherty DK, Buckman CT, Thompson MM, Matlock BK, Weller K, Ellacott KL (2014) Obesity induced by a high-fat diet is associated with increased immune cell entry into the central nervous system. Brain Behav Immun 35:33–42

    Article  CAS  PubMed  Google Scholar 

  • Cabral P, Meyer HB, Ames D (2011) Effectiveness of yoga therapy as a complementary treatment for major psychiatric disorders: a meta-analysis. Prim Care Companion CNS Disord 13(4)

    Google Scholar 

  • Cai D (2012) One step from prediabetes to diabetes: hypothalamic inflammation? Endocrinology 153(3):1010

    Google Scholar 

  • Cai D (2013) Neuroinflammation and neurodegeneration in overnutrition-induced diseases. Trends Endocrinol Metab 24(1):40–47

    Article  CAS  PubMed  Google Scholar 

  • Cai D, Liu T (2011) Hypothalamic inflammation: a double-edged sword to nutritional diseases. Ann N Y Acad Sci 1243(1):E1–E39

    Article  PubMed  PubMed Central  Google Scholar 

  • Cai D, Liu T (2012) Inflammatory cause of metabolic syndrome via brain stress and NF-κB. Aging (Albany NY) 4(2):98

    Article  CAS  Google Scholar 

  • Çakir I, Cyr NE, Perello M, Litvinov BP, Romero A, Stuart RC, Nillni EA (2013) Obesity induces hypothalamic endoplasmic reticulum stress and impairs proopiomelanocortin (POMC) post-translational processing. J Biol Chem 288(24):17675–17688

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Calle EE, Kaaks R (2004) Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 4(8):579–591

    Article  CAS  PubMed  Google Scholar 

  • Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ (2003) Overweight, obesity, and mortality from cancer in a prospectively studied cohort of US adults. N Engl J Med 348(17):1625–1638

    Article  PubMed  Google Scholar 

  • Castro G, Areias MFC, Weissmann L, Quaresma PG, Katashima CK, Saad MJ, Prada PO (2013) Diet-induced obesity induces endoplasmic reticulum stress and insulin resistance in the amygdala of rats. FEBS open bio 3:443–449

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cattin L, Bordin P, Fonda M, Adamo C, Barbone F, Bovenzi M, Manto A, Pedone C, Pahor M (1997) Factors associated with cognitive impairment among older Italian inpatients. J Am Geriatr Soc 45(11):1324–1330

    Article  CAS  PubMed  Google Scholar 

  • Chacón F, Mora F, Gervás-Ríos A, Gilaberte I (2011) Efficacy of lifestyle interventions in physical health management of patients with severe mental illness. Ann Gen Psychiatry 10(22):21929761

    Google Scholar 

  • Challis BG, Pritchard LE, Creemers JW, Delplanque J, Keogh JM, Luan JA, Wareham NJ, Yeo GS, Bhattacharyya S, Froguel P, White A (2002) A missense mutation disrupting a dibasic prohormone processing site in pro-opiomelanocortin (POMC) increases susceptibility to early-onset obesity through a novel molecular mechanism. Hum Mol Genet 11(17):1997–2004

    Article  CAS  PubMed  Google Scholar 

  • Clément K, Vaisse C, Lahlou N, Cabrol S, Pelloux V, Cassuto D, Gourmelen M, Dina C, Chambaz J, Lacorte JM, Basdevant A (1998) A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 392(6674):398–401

    Article  PubMed  Google Scholar 

  • Davidson S, Judd F, Jolley D, Hocking B, Thompson S (2000) The general health status of people with mental illness. Australas Psychiatry 8(1):31–35

    Article  Google Scholar 

  • Deng J, Lu PD, Zhang Y, Scheuner D, Kaufman RJ, Sonenberg N, Harding HP, Ron D (2004) Translational repression mediates activation of nuclear factor kappa B by phosphorylated translation initiation factor 2. Mol Cell Biol 24(23):10161–10168

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Du M, Yan X, Tong JF, Zhao J, Zhu MJ (2010) Maternal obesity, inflammation, and fetal skeletal muscle development. Biol Reprod 82(1):4–12

    Article  CAS  PubMed  Google Scholar 

  • Elias MF, Elias PK, Sullivan LM, Wolf PA, D’agostino RB (2003) Lower cognitive function in the presence of obesity and hypertension: the Framingham heart study. International journal of obesity 27(2):260–268

    Article  CAS  PubMed  Google Scholar 

  • Erion JR, Wosiski-Kuhn M, Dey A, Hao S, Davis CL, Pollock NK, Stranahan AM (2014) Obesity elicits interleukin 1-mediated deficits in hippocampal synaptic plasticity. J Neurosci 34(7):2618–2631

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Farooqi IS (2006) Monogenic human obesity syndromes. Prog Brain Res 153:119–125

    Article  CAS  PubMed  Google Scholar 

  • Farooqi IS, Rahilly O (2004) Monogenic human obesity syndromes. Recent Prog Horm Res 59:409–424

    Article  CAS  PubMed  Google Scholar 

  • Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, Perry JR, Elliott KS, Lango H, Rayner NW, Shields B (2007) A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316(5826):889–894

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fung TT, Rimm EB, Spiegelman D, Rifai N, Tofler GH, Willett WC, Hu FB (2001) Association between dietary patterns and plasma biomarkers of obesity and cardiovascular disease risk. Am J Clin Nutr 73(1):61–67

    CAS  PubMed  Google Scholar 

  • Gariepy G, Nitka D, Schmitz N (2010) The association between obesity and anxiety disorders in the population: a systematic review and meta-analysis. Int J Obes 34(3):407–419

    Article  CAS  Google Scholar 

  • Gauhar R, Hwang SL, Jeong SS, Kim JE, Song H, Park DC, Song KS, Kim TY, Oh WK, Huh TL (2012) Heat-processed Gynostemma pentaphyllum extract improves obesity in ob/ob mice by activating AMP-activated protein kinase. Biotechnol Lett 34(9):1607–1616

    Article  CAS  PubMed  Google Scholar 

  • Geller F, Reichwald K, Dempfle A, Illig T, Vollmert C, Herpertz S, Siffert W, Platzer M, Hess C, Gudermann T, Biebermann H (2004) Melanocortin-4 receptor gene variant I103 is negatively associated with obesity. Am J Hum Genet 74(3):572–581

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ghosh G, Wang VYF, Huang DB, Fusco A (2012) NF-κB regulation: lessons from structures. Immunol Rev 246(1):36–58

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Green AI, Drake RE, Brunette MF, Noordsy DL (2007) Schizophrenia and co-occurring substance use disorder. Am J Psychiatry 164(3):402–408

    Article  PubMed  Google Scholar 

  • Gregor MF, Hotamisligil GS (2011) Inflammatory mechanisms in obesity. Annu Rev Immunol 29:415–445

    Article  CAS  PubMed  Google Scholar 

  • Gunstad J, Paul RH, Cohen RA, Tate DF, Spitznagel MB, Gordon E (2007) Elevated body mass index is associated with executive dysfunction in otherwise healthy adults. Compr Psychiatry 48(1):57–61

    Article  PubMed  Google Scholar 

  • Guyenet PG (2006) The sympathetic control of blood pressure. Nat Rev Neurosci 7(5):335–346

    Article  CAS  PubMed  Google Scholar 

  • Haddad PM, Sharma SG (2007) Adverse effects of atypical antipsychotics. CNS drugs 21(11):911–936

    Article  CAS  PubMed  Google Scholar 

  • Halliwell B (2001) Role of free radicals in the neurodegenerative diseases. Drugs Aging 18(9):685–716

    Article  CAS  PubMed  Google Scholar 

  • Hashimoto T, Cook WS, Qi C, Yeldandi AV, Reddy JK, Rao MS (2000) Defect in peroxisome proliferator-activated receptor α-inducible fatty acid oxidation determines the severity of hepatic steatosis in response to fasting. J Biol Chem 275(37):28918–28928

    Article  CAS  PubMed  Google Scholar 

  • He G, Yu GY, Temkin V, Ogata H, Kuntzen C, Sakurai T, Sieghart W, Peck-Radosavljevic M, Leffert HL, Karin M (2010) Hepatocyte IKKβ/NF-κB inhibits tumor promotion and progression by preventing oxidative stress-driven STAT3 activation. Cancer Cell 17(3):286–297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Herbert A, Gerry NP, McQueen MB, Heid IM, Pfeufer A, Illig T, Wichmann HE, Meitinger T, Hunter D, Hu FB, Colditz G (2006) A common genetic variant is associated with adult and childhood obesity. Science 312(5771):279–283

    Article  CAS  PubMed  Google Scholar 

  • Herrera BM, Lindgren CM (2010) The genetics of obesity. Curr DiabRep 10(6):498–505

    Article  CAS  Google Scholar 

  • Hinney A, Schmidt A, Nottebom K, Heibult O, Becker I, Ziegler A, Gerber G, Sina M, Gorg T, Mayer H, Siegfried W (1999) Several mutations in the melanocortin-4 receptor gene including a nonsense and a frameshift mutation associated with dominantly inherited obesity in humans. J Clin Endocrinol Metab 84(4):1483–1486

    Article  CAS  PubMed  Google Scholar 

  • Hinney A, Vogel CI, Hebebrand J (2010) From monogenic to polygenic obesity: recent advances. Eur Child Adolesc Psychiatry 19(3):297–310

    Article  PubMed  PubMed Central  Google Scholar 

  • Horton TJ, Drougas H, Brachey A, Reed GW, Peters JC, Hill JO (1995) Fat and carbohydrate overfeeding in humans: different effects on energy storage. Am J Clin Nutr 62(1):19–29

    CAS  PubMed  Google Scholar 

  • Hu P, Han Z, Couvillon AD, Kaufman RJ, Exton JH (2006) Autocrine tumor necrosis factor alpha links endoplasmic reticulum stress to the membrane death receptor pathway through IRE1α-mediated NF-κB activation and down-regulation of TRAF2 expression. Mol Cell Biol 26(8):3071–3084

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hursting SD, Dunlap SM (2012) Obesity, metabolic dysregulation, and cancer: a growing concern and an inflammatory (and microenvironmental) issue. Ann N Y Acad Sci 1271(1):82–87

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jakabek D, Quirk F, Driessen M, Aljeesh Y, Baune BT (2011) Obesity and nutrition behaviours in Western and Palestinian outpatients with severe mental illness. BMC Psychiatry 11(1):159

    Article  PubMed Central  PubMed  Google Scholar 

  • Kamimura D, Ishihara K, Hirano T (2003) IL-6 signal transduction and its physiological roles: the signal orchestration model. In: Reviews of physiology, biochemistry and pharmacology. Springer, Berlin, pp 1–38

    Google Scholar 

  • Kang YM, Ma Y, Zheng JP, Elks C, Sriramula S, Yang ZM, Francis J (2009) Brain nuclear factor-kappa B activation contributes to neurohumoral excitation in angiotensin II-induced hypertension. Cardiovasc Res cvp073

    Google Scholar 

  • Kanoski SE, Zhang Y, Zheng W, Davidson TL (2010) The effects of a high-energy diet on hippocampal function and blood-brain barrier integrity in the rat. J Alzheimers Dis 21(1):207

    CAS  PubMed  PubMed Central  Google Scholar 

  • Karhunen LJ, Lappalainen RI, Vanninen EJ, Kuikka JT, Uusitupa MIJ (1997) Regional cerebral blood flow during food exposure in obese and normal weight women. Brain 120(9):1675–1684

    Article  PubMed  Google Scholar 

  • Kluge W, Alsaif M, Guest PC, Schwarz E, Bahn S (2011) Translating potential biomarker candidates for schizophrenia and depression to animal models of psychiatric disorders

    Google Scholar 

  • Knöchel C, Oertel-Knöchel V, O’Dwyer L, Prvulovic D, Alves G, Kollmann B, Hampel H (2012) Cognitive and behavioural effects of physical exercise in psychiatric patients. Prog Neurobiol 96(1):46–68

    Article  PubMed  Google Scholar 

  • Koide CL, Collier AC, Berry MJ, Panee J (2011) The effect of bamboo extract on hepatic biotransforming enzymes–findings from an obese–diabetic mouse model. J Ethnopharmacol 133(1):37–45

    Article  PubMed  Google Scholar 

  • Kousta E, Hadjiathanasiou CG, Tolis G, Papathanasiou A (2009) Pleiotropic genetic syndromes with developmental abnormalities associated with obesity. J Pediatr Endocrinol Metab 22(7):581–592

    Article  CAS  PubMed  Google Scholar 

  • Krogh-Madsen R, Plomgaard P, Møller K, Mittendorfer B, Pedersen BK (2006) Influence of TNF-α and IL-6 infusions on insulin sensitivity and expression of IL-18 in humans. Am J Physiol Endocrinol Metab 291(1):E108–E114

    Article  CAS  PubMed  Google Scholar 

  • Lalouel JM, Rao DC, Morton NE, Elston RC (1983) A unified model for complex segregation analysis. Am J Hum Genet 35(5):816

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lee JY, Sohn KH, Rhee SH, Hwang D (2001) Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through Toll-like receptor 4. J Biol Chem 276(20):16683–16689

    Article  CAS  PubMed  Google Scholar 

  • Li W, Prakash R, Chawla D, Du W, Didion SP, Filosa JA, Zhang Q, Brann DW, Lima VV, Tostes RC, Ergul A (2013) Early effects of high-fat diet on neurovascular function and focal ischemic brain injury. Am J Physiol Regul Integr Compar Physiol 304(11):R1001–R1008

    Article  CAS  Google Scholar 

  • Lin WW, Karin M (2007) A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest 117(5):1175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Linker R, Kleinewietfeld M, Lee DH, Muller D, Manzel A (2014) Dietary saturated fatty acids promote differentiation of Th1 and Th17 cells and aggravate neuroinflammation. Neurology, 82(10 Supplement):6–149

    Google Scholar 

  • Lumeng CN, Bodzin JL, Saltiel AR (2007) Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 117(1):175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maayan L, Hoogendoorn C, Sweat V, Convit A (2011) Disinhibited eating in obese adolescents is associated with orbitofrontal volume reductions and executive dysfunction. Obesity 19(7):1382–1387

    Article  PubMed  PubMed Central  Google Scholar 

  • Maes HH, Neale MC, Eaves LJ (1997) Genetic and environmental factors in relative body weight and human adiposity. Behav Genet 27(4):325–351

    Article  CAS  PubMed  Google Scholar 

  • Martins-de-Souza D, Maccarrone G, Wobrock T, Zerr I, Gormanns P, Reckow S, Falkai P, Schmitt A, Turck CW (2010a) Proteome analysis of the thalamus and cerebrospinal fluid reveals glycolysis dysfunction and potential biomarkers candidates for schizophrenia. J Psychiatr Res 44(16):1176–1189

    Article  PubMed  Google Scholar 

  • Martins-De-Souza D, Dias-Neto E, Schmitt A, Falkai P, Gormanns P, Maccarrone G, Turck CW, Gattaz WF (2010b) Proteome analysis of schizophrenia brain tissue. World J Biol Psychiatry 11(2):110–120

    Article  PubMed  Google Scholar 

  • Marwaha S, Johnson S, Bebbington P, Angermeyer MC, Brugha T, Azorin JM, Kilian R, Kornfeld A, Toumi M, EuroSC Study Group (2008) Correlates of subjective quality of life in people with schizophrenia: findings from the EuroSC study. J Nerv Mental Dis 196(2):87–94

    Google Scholar 

  • McNay DE, Briançon N, Kokoeva MV, Maratos-Flier E, Flier JS (2012) Remodeling of the arcuate nucleus energy-balance circuit is inhibited in obese mice. J Clin Investig 122(1):142

    Article  CAS  PubMed  Google Scholar 

  • Meng Q, Cai D (2011) Defective hypothalamic autophagy directs the central pathogenesis of obesity via the IκB kinase β (IKKβ)/NF-κB pathway. J Biol Chem 286(37):32324–32332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller AA, Spencer SJ (2014) Obesity and neuroinflammation: a pathway to cognitive impairment. Brain Behav Immun 42:10–21

    Google Scholar 

  • Molteni R, Barnard RJ, Ying Z, Roberts CK, Gomez-Pinilla F (2002) A high-fat, refined sugar diet reduces hippocampal brain-derived neurotrophic factor, neuronal plasticity, and learning. Neuroscience 112(4):803–814

    Article  CAS  PubMed  Google Scholar 

  • Moraes JC, Coope A, Morari J, Cintra DE, Roman EA, Pauli JR, Romanatto T, Carvalheira JB, Oliveira AL, Saad MJ, Velloso LA (2009) High-fat diet induces apoptosis of hypothalamic neurons. PLoS One 4(4):e5045

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mueller K, Anwander A, Möller HE, Horstmann A, Lepsien J, Busse F, Mohammadi S, Schroeter ML, Stumvoll M, Villringer A, Pleger B (2011) Sex-dependent influences of obesity on cerebral white matter investigated by diffusion-tensor imaging. PLoS One 6(4):e18544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Naugler WE, Sakurai T, Kim S, Maeda S, Kim K, Elsharkawy AM, Karin M (2007) Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science 317(5834):121–124

    Article  CAS  PubMed  Google Scholar 

  • Nerurkar PV, Johns LM, Buesa LM, Kipyakwai G, Volper E, Sato R, Shah P, Feher D, Williams PG, Nerurkar VR (2011) Momordica charantia (bitter melon) attenuates high-fat diet-associated oxidative stress and neuroinflammation. J Neuroinflammation 8(64):2094–2098

    Google Scholar 

  • Nguyen JC, Killcross AS, Jenkins TA (2014) Obesity and cognitive decline: role of inflammation and vascular changes. Front Neurosci 8:375

    Google Scholar 

  • Odegaard JI, Chawla A (2011) Alternative macrophage activation and metabolism. Ann Rev Pathol 6:275

    Article  CAS  Google Scholar 

  • Oeckinghaus A, Hayden MS, Ghosh S (2011) Crosstalk in NF-[kappa] B signaling pathways. Nat Immunol 12(8):695–708

    Article  CAS  PubMed  Google Scholar 

  • Pan DA, Lillioja S, Kriketos AD, Milner MR, Baur LA, Bogardus C, Jenkins AB, Storlien LH (1997) Skeletal muscle triglyceride levels are inversely related to insulin action. Diabetes 46(6):983–988

    Article  CAS  PubMed  Google Scholar 

  • Park EJ, Lee JH, Yu GY, He G, Ali SR, Holzer RG, Österreicher CH, Takahashi H, Karin M (2010) Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression. Cell 140(2):197–208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Paton JF, Waki H (2009) Is neurogenic hypertension related to vascular inflammation of the brainstem? Neurosci Biobehav Rev 33(2):89–94

    Article  CAS  PubMed  Google Scholar 

  • Pawar P, Gilda S, Sharma S, Jagtap S, Paradkar A, Mahadik K, Ranjekar P, Harsulkar A (2011) Rectal gel application of Withania somnifera root extract expounds anti-inflammatory and muco-restorative activity in TNBS-induced Inflammatory Bowel Disease. BMC Complement Altern Med 11(1):34

    Article  PubMed  PubMed Central  Google Scholar 

  • Pepping JK, Freeman LR, Gupta S, Keller JN, Bruce-Keller AJ (2013) NOX2 deficiency attenuates markers of adiposopathy and brain injury induced by high-fat diet. Am J Physiol Endocrinol Metab 304(4):E392–E404

    Article  CAS  PubMed  Google Scholar 

  • Pilch PF, Lee J (2004) Insulin receptor family. Encyclopedia Biol Chem 2:436–440

    Article  CAS  Google Scholar 

  • Popkin BM, Gordon-Larsen P (2004) The nutrition transition: worldwide obesity dynamics and their determinants. Int J Obes 28:S2–S9

    Article  Google Scholar 

  • Purkayastha S, Zhang H, Zhang G, Ahmed Z, Wang Y, Cai D (2011) Neural dysregulation of peripheral insulin action and blood pressure by brain endoplasmic reticulum stress. Proc Natl Acad Sci 108(7):2939–2944

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rahmouni K, Correia ML, Haynes WG, Mark AL (2005) Obesity-associated hypertension new insights into mechanisms. Hypertension 45(1):9–14

    Article  CAS  PubMed  Google Scholar 

  • Raji CA, Ho AJ, Parikshak NN, Becker JT, Lopez OL, Kuller LH, Hua X, Leow AD, Toga AW, Thompson PM (2010) Brain structure and obesity. Hum Brain Mapp 31(3):353–364

    PubMed  PubMed Central  Google Scholar 

  • Rao RV, Ellerby HM, Bredesen DE (2004) Coupling endoplasmic reticulum stress to the cell death program. Cell Death Differ 11(4):372–380

    Article  CAS  PubMed  Google Scholar 

  • Rao SM, Reddy JK (2004) PPARα in the pathogenesis of fatty liver disease. Hepatology 40(4):783–786

    Article  CAS  PubMed  Google Scholar 

  • Reilly JJ, Armstrong J, Dorosty AR, Emmett PM, Ness A, Rogers I, Steer C, Sherriff A (2005) Early life risk factors for obesity in childhood: cohort study. BMJ 330(7504):1357

    Article  PubMed  PubMed Central  Google Scholar 

  • Rivera P, Pérez-Martín M, Pavón FJ, Serrano A, Crespillo A, Cifuentes M, López-Ávalos MD, Grondona JM, Vida M, Fernández-Llebrez P, de Fonseca FR (2013) Pharmacological administration of the isoflavone daidzein enhances cell proliferation and reduces high fat diet-induced apoptosis and gliosis in the rat hippocampus. PLoS One 8(5):e64750

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ron D, Walter P (2007) Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol 8(7):519–529

    Article  CAS  PubMed  Google Scholar 

  • Rummel-Kluge C, Komossa K, Schwarz S, Hunger H, Schmid F, Lobos CA, Kissling W, Davis JM, Leucht S (2010) Head-to-head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: a systematic review and meta-analysis. Schizophr Res 123(2):225–233

    Article  PubMed  PubMed Central  Google Scholar 

  • Russell JC, Graham SE, Richardson M (1998) Cardiovascular disease in the JCR: LA-cp rat. Mol Cell Biochem 188(1–2):113–126

    Article  CAS  PubMed  Google Scholar 

  • Sabia S, Kivimaki M, Shipley MJ, Marmot MG, Singh-Manoux A (2009) Body mass index over the adult life course and cognition in late midlife: the Whitehall II Cohort Study. Am J Clin Nutr 89(2):601–607

    Article  CAS  PubMed  Google Scholar 

  • Saghizadeh M, Ong JM, Garvey WT, Henry RR, Kern PA (1996) The expression of TNF alpha by human muscle. Relationship to insulin resistance. J Clin Inv 97(4):1111

    Article  CAS  Google Scholar 

  • Sakurai T, He G, Matsuzawa A, Yu GY, Maeda S, Hardiman G, Karin M (2008) Hepatocyte necrosis induced by oxidative stress and IL-1α release mediate carcinogen-induced compensatory proliferation and liver tumorigenesis. Cancer Cell 14(2):156–165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schillaci G, Pirro M, Gemelli F, Pasqualini L, Vaudo G, Marchesi S, Siepi D, Bagaglia F, Mannarino E (2003) Increased C-reactive protein concentrations in never-treated hypertension: the role of systolic and pulse pressures. J Hypertens 21(10):1841–1846

    Article  CAS  PubMed  Google Scholar 

  • Shi P, Diez-Freire C, Jun JY, Qi Y, Katovich MJ, Li Q, Sriramula S, Francis J, Sumners C, Raizada MK (2010) Brain microglial cytokines in neurogenic hypertension. Hypertension 56(2):297–303

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shoelson SE, Herrero L, Naaz A (2007) Obesity, inflammation, and insulin resistance. Gastroenterology 132(6):2169–2180

    Article  CAS  PubMed  Google Scholar 

  • Shu CJ, Benoist C, Mathis D (2012) The immune system’s involvement in obesity-driven type 2 diabetes. In: Seminars in immunology, vol 24, no 6. Academic Press, pp 436–442

    Google Scholar 

  • Simoneau JA, Colberg SR, Thaete FL, Kelley DE (1995) Skeletal muscle glycolytic and oxidative enzyme capacities are determinants of insulin sensitivity and muscle composition in obese women. FASEB J 9(2):273–278

    CAS  PubMed  Google Scholar 

  • Slentz CA, Houmard JA, Kraus WE (2009) Exercise, abdominal obesity, skeletal muscle, and metabolic risk: evidence for a dose response. Obesity 17(S3):S27–S33

    Article  PubMed  PubMed Central  Google Scholar 

  • Sokal J, Messias E, Dickerson FB, Kreyenbuhl J, Brown CH, Goldberg RW, Dixon LB (2004) Comorbidity of medical illnesses among adults with serious mental illness who are receiving community psychiatric services. J Nerv Ment Dis 192(6):421–427

    Article  PubMed  Google Scholar 

  • Solinas G, Karin M (2010) JNK1 and IKKβ: molecular links between obesity and metabolic dysfunction. FASEB J 24(8):2596–2611

    Article  CAS  PubMed  Google Scholar 

  • Sorensen TI, Echwald S, Holm JC (1996) Leptin in obesity. BMJ. Br Med J 313(7063):953

    Google Scholar 

  • Speakman JR, Rance KA, Johnstone AM (2008) Polymorphisms of the FTO gene are associated with variation in energy intake, but not energy expenditure. Obesity 16(8):1961–1965

    Article  CAS  PubMed  Google Scholar 

  • Strobel A, Issad T, Camoin L, Ozata M, Strosberg AD (1998) A leptin missense mutation associated with hypogonadism and morbid obesity. Nat genet 18(3):213–215

    Google Scholar 

  • Stumpf C, John S, Jukic J, Yilmaz A, Raaz D, Schmieder RE, Daniel WG, Garlichs CD (2005) Enhanced levels of platelet P-selectin and circulating cytokines in young patients with mild arterial hypertension. J Hypertens 23(5):995–1000

    Article  CAS  PubMed  Google Scholar 

  • Stutzmann F, Vatin V, Cauchi S, Morandi A, Jouret B, Landt O, Tounian P, Levy-Marchal C, Buzzetti R, Pinelli L, Balkau B (2007) Non-synonymous polymorphisms in melanocortin-4 receptor protect against obesity: the two facets of a Janus obesity gene. Hum Mol Genet 16(15):1837–1844

    Article  CAS  PubMed  Google Scholar 

  • Taki Y, Kinomura S, Sato K, Inoue K, Goto R, Okada K, Uchida S, Kawashima R, Fukuda H (2008) Relationship between body mass index and gray matter volume in 1428 healthy individuals. Obesity 16(1):119–124

    Article  PubMed  Google Scholar 

  • Tanaka S, Takehashi M, Matoh N, Iida S, Suzuki T, Futaki S, Hamada H, Masliah E, Sugiura Y, Ueda K (2002) Generation of reactive oxygen species and activation of NF-κB by non-Aβ component of Alzheimer’s disease amyloid. J Neurochem 82(2):305–315

    Article  CAS  PubMed  Google Scholar 

  • Timmermans S, Bogie JF, Vanmierlo T, Lütjohann D, Stinissen P, Hellings N, Hendriks JJ (2014) High fat diet exacerbates neuroinflammation in an animal model of multiple sclerosis by activation of the renin angiotensin system. J Neuroimmune Pharmacol 9(2):209–217

    Google Scholar 

  • Tomassoni D, Nwankwo IE, Gabrielli MG, Bhatt S, Muhammad AB, Lokhandwala MF, Tayebati SK, Amenta F (2013) Astrogliosis in the brain of obese Zucker rat: a model of metabolic syndrome. Neurosci Lett 543:136–141

    Article  CAS  PubMed  Google Scholar 

  • Vaisse C, Clement K, Durand E, Hercberg S, Guy-Grand B, Froguel P (2000) Melanocortin-4 receptor mutations are a frequent and heterogeneous cause of morbid obesity. J Clin Inv 106(2):253

    Article  CAS  Google Scholar 

  • van Dam RM, Willett WC, Rimm EB, Stampfer MJ, Hu FB (2002) Dietary fat and meat intake in relation to risk of type 2 diabetes in men. Diab Care 25(3):417–424

    Article  Google Scholar 

  • Wang X, Bao W, Liu J, OuYang YY, Wang D, Rong S, Xiao X, Shan ZL, Zhang Y, Yao P, Liu LG (2013) Inflammatory markers and risk of type 2 diabetes. Diabetes care 36(1):166–175

    Google Scholar 

  • Wang Z, Liu D, Wang F, Liu S, Zhao S, Ling EA, Hao A (2012a) Saturated fatty acids activate microglia via toll-like receptor 4/NF-κB signalling. Br J Nutr 107(02):229–241

    Article  CAS  PubMed  Google Scholar 

  • Wang Z, Liu D, Wang F, Liu S, Zhao S, Ling EA, Hao A (2012b) Saturated fatty acids activate microglia via toll-like receptor 4/NF-κB signalling. Br J Nutr 107(02):229–241

    Article  CAS  PubMed  Google Scholar 

  • Ward MA, Carlsson CM, Trivedi MA, Sager MA, Johnson SC (2005) The effect of body mass index on global brain volume in middle-aged adults: a cross sectional study. BMC neurol 5(1):1

    Google Scholar 

  • Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Inv 112(12):1796

    Article  CAS  Google Scholar 

  • White MF (2003) Insulin signaling in health and disease. Science 302(5651):1710–1711

    Article  CAS  PubMed  Google Scholar 

  • Williams LM (2012) Hypothalamic dysfunction in obesity. Proc Nutr Soc 71(04):521–533

    Article  CAS  PubMed  Google Scholar 

  • Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Inv 112(12):1821

    Article  CAS  Google Scholar 

  • Yamazaki H, Hiramatsu N, Hayakawa K, Tagawa Y, Okamura M, Ogata R, Huang T, Nakajima S, Yao J, Paton AW, Paton JC (2009) Activation of the Akt-NF-κB pathway by subtilase cytotoxin through the ATF6 branch of the unfolded protein response. J Immunol 183(2):1480–1487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yau PL, Castro MG, Tagani A, Tsui WH, Convit A (2012) Obesity and metabolic syndrome and functional and structural brain impairments in adolescence. Pediatrics 130(4):e856–e864

    Article  PubMed Central  PubMed  Google Scholar 

  • Yeo GS, Farooqi IS, Aminian S, Halsall DJ, Stanhope RG, O’Rahilly S (1998) A frameshift mutation in MC4R associated with dominantly inherited human obesity. Nat Genet 20(2):111–112

    Article  CAS  PubMed  Google Scholar 

  • Yi CX, Gericke M, Krüger M, Alkemade A, Kabra DG, Hanske S, Filosa J, Pfluger P, Bingham N, Woods SC, Herman J (2012) High calorie diet triggers hypothalamic angiopathy. Mol Metab 1(1):95–100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yokum S, Ng J, Stice E (2012) Relation of regional gray and white matter volumes to current BMI and future increases in BMI: a prospective MRI study. Int J Obes 36(5):656–664

    Article  CAS  Google Scholar 

  • Zambrano E, Martínez-Samayoa PM, Bautista CJ, Deas M, Guillen L, Rodríguez-González GL, Guzman C, Larrea F, Nathanielsz PW (2005) Sex differences in transgenerational alterations of growth and metabolism in progeny (F2) of female offspring (F1) of rats fed a low protein diet during pregnancy and lactation. J Physiol 566(1):225–236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang X, Dong F, Ren J, Driscoll MJ, Culver B (2005) High dietary fat induces NADPH oxidase-associated oxidative stress and inflammation in rat cerebral cortex. Exp Neurol 191(2):318–325

    Article  CAS  PubMed  Google Scholar 

  • Zhang X, Zhang G, Zhang H, Karin M, Bai H, Cai D (2008) Hypothalamic IKKβ/NF-κB and ER stress link overnutrition to energy imbalance and obesity. Cell 135(1):61–73

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou R, Yazdi AS, Menu P, Tschopp J (2011) A role for mitochondria in NLRP3 inflammasome activation. Nature 469(7329):221–225

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Biotechnology, Guru Nanak Dev University, Amritsar, 143005, Punjab, India

    Gurcharan Kaur, Anuradha Sharma, Muskan Gupta & Taranjeet Kaur

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  1. Gurcharan Kaur
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  2. Anuradha Sharma
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  3. Muskan Gupta
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  4. Taranjeet Kaur
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Correspondence to Gurcharan Kaur .

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  1. Molecular and Cellular Neuroscience, National Brain Research Centre, Gurgaon, Delhi, India

    Nihar Jana

  2. Molecular and Cellular Neuroscience, National Brain Research Centre, Gurgaon, Delhi, India

    Anirban Basu

  3. National Brain Research Centre, National Research Professor, National Brain Research Centre, Gurgaon, Delhi, India

    Prakash Narain Tandon

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Kaur, G., Sharma, A., Gupta, M., Kaur, T. (2016). Obesity and Neuroinflammation. In: Jana, N., Basu, A., Tandon, P. (eds) Inflammation: the Common Link in Brain Pathologies. Springer, Singapore. https://doi.org/10.1007/978-981-10-1711-7_12

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