Antioxidant food supplements and obesity-related inflammation

Current Medicinal Chemistry

Volumn 20, Issue 18, 2013, Pages 2330-2337

  Mangge, H ^a   Summers, K ^a   Almer, G ^a   Prassl, R ^a   Weghuber, D ^b   Schnedl, W ^c   Fuchs, D ^d  

^a MEDICAL UNIVERSITY OF GRAZ   (Austria)

^b Paracelsus Private Medical School   (Austria)

^c Practice for General Internal Medicine   (Austria)

^d INNSBRUCK MEDICAL UNIVERSITY   (Austria)

Author keywords

Antioxidants; Food supplements; Inflammation; Leptin; Melatonin; Obesity; Oxidative stress; Serotonin; Th1; Tryptophan

Indexed keywords

ANTIOXIDANT; FOOD ADDITIVE; LEPTIN;

ADAPTIVE IMMUNITY; ADIPOCYTE; ARTICLE; DIET SUPPLEMENTATION; DRUG DEPENDENCE; FOOD INTAKE; HIPPOCAMPUS; INFLAMMATION; INSULIN RESISTANCE; INSULIN SENSITIVITY; NONHUMAN; OBESITY; OXIDATIVE STRESS; REWARD; TH1 CELL;

ADAPTIVE IMMUNITY; ANIMALS; ANTIOXIDANTS; FOOD ADDITIVES; HUMANS; INFLAMMATION; LEPTIN; OBESITY;

EID: 84877985409     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/0929867311320180004     Document Type: Article

References (112)

1. Califf, R. M. Key issues for global cardiovascular medicine. Lancet, 2009, 374(9689), 508-510.
2. Zimmet, P.; Alberti, K. G.; Shaw, J. Global and societal implications of the diabetes epidemic. Nature, 2001, 414(6865), 782-787.
3. Wang, Y.; Beydoun, M. A.; Liang, L.; Caballero, B.; Kumanyika, S. K. Will all Americans become overweight or obese? estimating the progression and cost of the US obesity epidemic. Obesity (Silver Spring), 2008, 16(10), 2323-2330.
4. Calle, E. E.; Thun, M. J.; Petrelli, J. M.; Rodriguez, C.; Heath, C. W., Jr. Body-mass index and mortality in a prospective cohort of U.S. adults. N. Engl. J. Med., 1999, 341(15), 1097-1105.
5. Cikim, A. S.; Ozbey, N.; Orhan, Y. Relationship between cardiovascular risk indicators and types of obesity in overweight and obese women. J. Int. Med. Res., 2004, 32(3), 268-273.
6. Fontaine, K. R.; Redden, D. T.; Wang, C.; Westfall, A. O.; Allison, D. B. Years of life lost due to obesity. JAMA, 2003, 289(2), 187-193.
7. Hu, F. B.; Willett, W. C.; Li, T.; Stampfer, M. J.; Colditz, G. A.; Manson, J. E. Adiposity as compared with physical activity in predicting mortality among women. N. Engl. J. Med., 2004, 351(26), 2694-2703.
8. Zaknun, D.; Schroecksnadel, S.; Kurz, K.; Fuchs, D. Potential role of antioxidant food supplements, preservatives and colorants in the pathogenesis of allergy and asthma. Int. Arch. Allergy Immunol., 2012, 157(2), 113-124.
9. Tan, P. H.; Sagoo, P.; Chan, C.; Yates, J. B.; Campbell, J.; Beutelspacher, S. C.; Foxwell, B. M.; Lombardi, G.; George, A. J. Inhibition of NF-kappa B and oxidative pathways in human dendritic cells by antioxidative vitamins generates regulatory T cells. J. Immunol., 2005, 174(12), 7633-7644.
10. Winkler, C.; Frick, B.; Schroecksnadel, K.; Schennach, H.; Fuchs, D. Food preservatives sodium sulfite and sorbic acid suppress mitogen-stimulated peripheral blood mononuclear cells. Food Chem. Toxicol., 2006, 44(12), 2003-2007.
11. Romagnani, S. Immunologic influences on allergy and the TH1/TH2 balance. J. Allergy Clin. Immunol., 2004, 113(3), 395-400.
12. Lucey, D. R.; Clerici, M.; Shearer, G. M. Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic, and inflammatory diseases. Clin. Microbiol. Rev., 1996, 9(4), 532-562.
13. Murr, C.; Schroecksnadel, K.; Winkler, C.; Ledochowski, M.; Fuchs, D. Antioxidants may increase the probability of developing allergic diseases and asthma. Med. Hypotheses, 2005, 64(5), 973-977.
14. Rocha, V. Z.; Folco, E. J.; Sukhova, G.; Shimizu, K.; Gotsman, I.; Vernon, A. H.; Libby, P. Interferon-gamma, a Th1 cytokine, regulates fat inflammation: a role for adaptive immunity in obesity. Circ. Res., 2008, 103(5), 467-476.
15. Schroecksnadel, K.; Fischer, B.; Schennach, H.; Weiss, G.; Fuchs, D. Antioxidants suppress Th1-type immune response in vitro. Drug. Metab. Lett., 2007, 1(3), 166-171.
16. McCall, M. R.; Frei, B. Can antioxidant vitamins materially reduce oxidative damage in humans? Free Radic. Biol. Med., 1999, 26(7-8), 1034-1053.
17. Poljsak, B.; Milisav, I. The neglected significance of "antioxidative stress". Oxid. Med. Cell. Longev., 2012, 2012, 480895.
18. Bjelakovic, G.; Nikolova, D.; Gluud, L. L.; Simonetti, R. G.; Gluud, C. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-Analysis. JAMA, 2007, 297(8), 842-857.
19. Bjelakovic, G.; Gluud, C. Surviving antioxidant supplements. J. Natl. Cancer Inst., 2007, 99(10), 742-743.
20. Bjelakovic, G.; Nikolova, D.; Simonetti, R. G.; Gluud, C. Antioxidant supplements for preventing gastrointestinal cancers. Cochrane Database Syst. Rev., 2004, (4), CD004183.
21. Bjelakovic, G.; Nikolova, D.; Simonetti, R. G.; Gluud, C. Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-Analysis. Lancet, 2004, 364(9441), 1219-1228.
22. Caraballoso, M.; Sacristan, M.; Serra, C.; Bonfill, X. Drugs for preventing lung cancer in healthy people. Cochrane Database Syst. Rev., 2003, (2), CD002141.
23. Vivekananthan, D. P.; Penn, M. S.; Sapp, S. K.; Hsu, A.; Topol, E. J. Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-Analysis of randomised trials. Lancet, 2003, 361(9374), 2017-2023.
24. Volkow, N. D.; Wang, G. J.; Tomasi, D.; Baler, R. D. Obesity and addiction: neurobiological overlaps. Obes. Rev., 2012.
25. Smith, G. P. The controls of eating: a shift from nutritional homeostasis to behavioral neuroscience. Nutrition, 2000, 16(10), 814-820.
26. Karasz, A. B.; Maxstadt, J. J.; Reher, J.; Decocco, F. Rapid screening procedure for the determination of preservatives in ground beef: sulfites, benzoates, sorbates, and ascorbates. J. Assoc. Off. Anal. Chem., 1976, 59(4), 766-769.
27. Luck, E. Food applications of sorbic acid and its salts. Food Addit. Contam., 1990, 7(5), 711-715.
28. Mangge, H.; Almer, G.; Truschnig-Wilders, M.; Schmidt, A.; Gasser, R.; Fuchs, D. Inflammation, adiponectin, obesity and cardiovascular risk. Curr. Med. Chem., 2010, 17(36), 4511-4520.
29. Mangge, H.; Schauenstein, K.; Stroedter, L.; Griesl, A.; Maerz, W.; Borkenstein, M. Low grade inflammation in juvenile obesity and type 1 diabetes associated with early signs of atherosclerosis. Exp. Clin. Endocrinol. Diabetes, 2004, 112(7), 378-382.
30. Cottam, D. R.; Mattar, S. G.; Barinas-Mitchell, E.; Eid, G.; Kuller, L.; Kelley, D. E.; Schauer, P. R. The chronic inflammatory hypothesis for the morbidity associated with morbid obesity: implications and effects of weight loss. Obes. Surg., 2004, 14(5), 589-600.
31. Mangge, H.; Kenzian, H.; Gallistl, S.; Neuwirth, G.; Liebmann, P.; Kaulfersch, W.; Beaufort, F.; Muntean, W.; Schauenstein, K. Serum cytokines in juvenile rheumatoid arthritis. Correlation with conventional inflammation parameters and clinical subtypes. Arthritis Rheum., 1995, 38(2), 211-220.
32. Toni, R.; Malaguti, A.; Castorina, S.; Roti, E.; Lechan, R. M. New paradigms in neuroendocrinology: relationships between obesity, systemic inflammation and the neuroendocrine system. J. Endocrinol. Invest., 2004, 27(2), 182-186.
33. Stelzer, I.; Zelzer, S.; Raggam, R. B.; Pruller, F.; Truschnig-Wilders, M.; Meinitzer, A.; Schnedl, W. J.; Horejsi, R.; Moller, R.; Weghuber, D.; Reeves, G.; Postolache, T. T.; Mangge, H. Link between leptin and interleukin-6 levels in the initial phase of obesity related inflammation. Transl. Res., 2012, 159(2), 118-124.
34. Farooqi, I. S.; Matarese, G.; Lord, G. M.; Keogh, J. M.; Lawrence, E.; Agwu, C.; Sanna, V.; Jebb, S. A.; Perna, F.; Fontana, S.; Lechler, R. I.; DePaoli, A. M.; O'Rahilly, S. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/ metabolic dysfunction of human congenital leptin deficiency. J. Clin. Invest., 2002, 110(8), 1093-1103.
35. Brandacher, G.; Hoeller, E.; Fuchs, D.; Weiss, H. G. Chronic immune activation underlies morbid obesity: is IDO a key player? Curr. Drug. Metab., 2007, 8(3), 289-295.
36. Mellor, A. L.; Munn, D. H. Tryptophan catabolism and regulation of adaptive immunity. J. Immunol., 2003, 170(12), 5809-5813.
37. Uyttenhove, C.; Pilotte, L.; Theate, I.; Stroobant, V.; Colau, D.; Parmentier, N.; Boon, T.; Van Den Eynde, B. J. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat. Med., 2003, 9(10), 1269-1274.
38. Murr, C.; Widner, B.; Wirleitner, B.; Fuchs, D. Neopterin as a marker for immune system activation. Curr. Drug. Metab., 2002, 3(2), 175-187.
39. Cascio, G.; Schiera, G.; Di Liegro, I. Dietary fatty acids in metabolic syndrome, diabetes and cardiovascular diseases. Curr. Diabetes Rev., 2012, 8(1), 2-17.
40. Riccardi, G.; Giacco, R.; Rivellese, A. A. Dietary fat, insulin sensitivity and the metabolic syndrome. Clin. Nutr., 2004, 23(4), 447-456.
41. Dandona, P.; Aljada, A.; Chaudhuri, A.; Mohanty, P.; Garg, R. Metabolic syndrome: a comprehensive perspective based on interactions between obesity, diabetes, and inflammation. Circulation, 2005, 111(11), 1448-1454.
42. Pacifico, L.; Di Renzo, L.; Anania, C.; Osborn, J. F.; Ippoliti, F.; Schiavo, E.; Chiesa, C. Increased T-helper interferon-gammasecreting cells in obese children. Eur. J. Endocrinol., 2006, 154(5), 691-697.
43. Considine, R. V.; Sinha, M. K.; Heiman, M. L.; Kriauciunas, A.; Stephens, T. W.; Nyce, M. R.; Ohannesian, J. P.; Marco, C. C.; McKee, L. J.; Bauer, T. L.; et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N. Engl. J. Med., 1996, 334(5), 292-295.
44. Saladin, R.; De Vos, P.; Guerre-Millo, M.; Leturque, A.; Girard, J.; Staels, B.; Auwerx, J. Transient increase in obese gene expression after food intake or insulin administration. Nature, 1995, 377(6549), 527-529.
45. Hamilton, B. S.; Paglia, D.; Kwan, A. Y.; Deitel, M. Increased obese mRNA expression in omental fat cells from massively obese humans. Nat. Med., 1995, 1(9), 953-956.
46. Anubhuti; Arora, S. Leptin and its metabolic interactions: an update. Diabetes Obes. Metab., 2008, 10(11), 973-993.
47. Jequier, E. Leptin signaling, adiposity, and energy balance. Ann. N. Y. Acad. Sci., 2002, 967, 379-388.
48. Ramos, E. J.; Meguid, M. M.; Campos, A. C.; Coelho, J. C. Neuropeptide Y, alpha-melanocyte-stimulating hormone, and monoamines in food intake regulation. Nutrition, 2005, 21(2), 269-279.
49. Flier, J. S. Hormone Resistance in Diabetes and Obesity: Insulin, Leptin, and FGF21. Yale J. Biol. Med., 2012, 85(3), 405-414.
50. Lago, R.; Gomez, R.; Lago, F.; Gomez-Reino, J.; Gualillo, O. Leptin beyond body weight regulation-current concepts concerning its role in immune function and inflammation. Cell Immunol., 2008, 252(1-2), 139-145.
51. Scarpace, P. J.; Zhang, Y. Leptin resistance: a prediposing factor for diet-induced obesity. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2009, 296(3), R493-500.
52. Maffei, M.; Halaas, J.; Ravussin, E.; Pratley, R. E.; Lee, G. H.; Zhang, Y.; Fei, H.; Kim, S.; Lallone, R.; Ranganathan, S.; et al. Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat. Med., 1995, 1(11), 1155-1161.
53. Heymsfield, S. B.; Greenberg, A. S.; Fujioka, K.; Dixon, R. M.; Kushner, R.; Hunt, T.; Lubina, J. A.; Patane, J.; Self, B.; Hunt, P.; McCamish, M. Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA, 1999, 282(16), 1568-1575.
54. Banks, W. A.; Kastin, A. J.; Huang, W.; Jaspan, J. B.; Maness, L. M. Leptin enters the brain by a saturable system independent of insulin. Peptides, 1996, 17(2), 305-311.
55. Caro, J. F.; Kolaczynski, J. W.; Nyce, M. R.; Ohannesian, J. P.; Opentanova, I.; Goldman, W. H.; Lynn, R. B.; Zhang, P. L.; Sinha, M. K.; Considine, R. V. Decreased cerebrospinal-fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance. Lancet, 1996, 348(9021), 159-161.
56. Schwartz, M. W.; Peskind, E.; Raskind, M.; Boyko, E. J.; Porte, D., Jr. Cerebrospinal fluid leptin levels: relationship to plasma levels and to adiposity in humans. Nat. Med., 1996, 2(5), 589-593.
57. Abhilash, M. Potential applications of Nanoparticles. IJPBS, 2010, 1(1), 12.
58. Vaisse, C.; Halaas, J. L.; Horvath, C. M.; Darnell, J. E., Jr.; Stoffel, M.; Friedman, J. M. Leptin activation of Stat3 in the hypothalamus of wild-type and ob/ob mice but not db/db mice. Nat. Genet., 1996, 14(1), 95-97.
59. Bjorbak, C.; Lavery, H. J.; Bates, S. H.; Olson, R. K.; Davis, S. M.; Flier, J. S.; Myers, M. G., Jr. SOCS3 mediates feedback inhibition of the leptin receptor via Tyr985. J. Biol. Chem., 2000, 275(51), 40649-40657.
60. Bjorbaek, C.; Buchholz, R. M.; Davis, S. M.; Bates, S. H.; Pierroz, D. D.; Gu, H.; Neel, B. G.; Myers, M. G., Jr.; Flier, J. S. Divergent roles of SHP-2 in ERK activation by leptin receptors. J. Biol. Chem., 2001, 276(7), 4747-4755.
61. Peruzzo, B.; Pastor, F. E.; Blazquez, J. L.; Schobitz, K.; Pelaez, B.; Amat, P.; Rodriguez, E. M. A second look at the barriers of the medial basal hypothalamus. Exp. Brain. Res., 2000, 132(1), 10-26.
62. Bates, S. H.; Myers, M. G., Jr. The role of leptin receptor signaling in feeding and neuroendocrine function. Trends. Endocrinol. Metab., 2003, 14(10), 447-452.
63. Ciardi, C.; Jenny, M.; Tschoner, A.; Ueberall, F.; Patsch, J.; Pedrini, M.; Ebenbichler, C.; Fuchs, D. Food additives such as sodium sulphite, sodium benzoate and curcumin inhibit leptin release in lipopolysaccharide-treated murine adipocytes in vitro. Br. J. Nutr., 2012, 107(6), 826-833.
64. Wirleitner, B.; Schroecksnadel, K.; Winkler, C.; Schennach, H.; Fuchs, D. Resveratrol suppresses interferon-gamma-induced bio chemical pathways in human peripheral blood mononuclear cells in vitro. Immunol. Lett., 2005, 100(2), 159-163.
65. Ristow, M.; Zarse, K.; Oberbach, A.; Kloting, N.; Birringer, M.; Kiehntopf, M.; Stumvoll, M.; Kahn, C. R.; Bluher, M. Antioxidants prevent health-promoting effects of physical exercise in humans. Proc. Natl. Acad. Sci. USA., 2009, 106(21), 8665-8670.
66. Powers, S. K.; Jackson, M. J. Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production. Physiol. Rev., 2008, 88(4), 1243-1276.
67. Peternelj, T. T.; Coombes, J. S. Antioxidant Supplementation during Exercise Training: Beneficial or Detrimental? Sports. Med., 2011.
68. Nduhirabandi, F.; du Toit, E. F.; Lochner, A. Melatonin and the metabolic syndrome: a tool for effective therapy in obesityassociated abnormalities? Acta. Physiol. (Oxf), 2012, 205(2), 209-223.
69. Brandacher, G.; Winkler, C.; Aigner, F.; Schwelberger, H.; Schroecksnadel, K.; Margreiter, R.; Fuchs, D.; Weiss, H. G. Bariatric surgery cannot prevent tryptophan depletion due to chronic immune activation in morbidly obese patients. Obes. Surg., 2006, 16(5), 541-548.
70. Blundell, J. E.; Lawton, C. L. Serotonin and dietary fat intake: effects of dexfenfluramine. Metabolism, 1995, 44(2 Suppl 2), 33-37.
71. Bray, G. A. Drug treatment of obesity. Rev. Endocr. Metab. Disord., 2001, 2(4), 403-418.
72. Halford, J. C.; Blundell, J. E. Separate systems for serotonin and leptin in appetite control. Ann. Med., 2000, 32(3), 222-232.
73. Hagan, M. M.; Holguin, F. D.; Cabello, C. E.; Hanscom, D. R.; Moss, D. E. Combined naloxone and fluoxetine on deprivationinduced binge eating of palatable foods in rats. Pharmacol. Biochem. Behav., 1997, 58(4), 1103-1107.
74. Buwalda, B.; Blom, W. A.; Koolhaas, J. M.; van Dijk, G. Behavioral and physiological responses to stress are affected by high-fat feeding in male rats. Physiol. Behav., 2001, 73(3), 371-377.
75. Murray, M. F. Tryptophan depletion and HIV infection: a metabo lic link to pathogenesis. Lancet Infect. Dis., 2003, 3(10), 644-652.
76. Wurtman, R. J.; Wurtman, J. J. Brain serotonin, carbohydratecraving, obesity and depression. Obes. Res., 1995, 3 Suppl 4, 477S-480S.
77. Ferry, G.; Ubeaud, C.; Lambert, P. H.; Bertin, S.; Coge, F.; Chomarat, P.; Delagrange, P.; Serkiz, B.; Bouchet, J. P.; Truscott, R. J.; Boutin, J. A. Molecular evidence that melatonin is enzymati cally oxidized in a different manner than tryptophan: investigations with both indoleamine 2,3-dioxygenase and myeloperoxidase. Biochem. J., 2005, 388(Pt 1), 205-215.
78. Van Cauter, E.; Knutson, K. L. Sleep and the epidemic of obesity in children and adults. Eur. J. Endocrinol., 2008, 159 Suppl 1, S59-66.
79. Cizza, G.; Requena, M.; Galli, G.; de Jonge, L. Chronic sleep deprivation and seasonality: implications for the obesity epidemic. J. Endocrinol. Invest., 2011, 34(10), 793-800.
80. Wu, M. F.; John, J.; Maidment, N.; Lam, H. A.; Siegel, J. M. Hypocretin release in normal and narcoleptic dogs after food and sleep deprivation, eating, and movement. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2002, 283(5), R1079-1086.
81. Estabrooke, I. V.; McCarthy, M. T.; Ko, E.; Chou, T. C.; Chemelli, R. M.; Yanagisawa, M.; Saper, C. B.; Scammell, T. E. Fos expression in orexin neurons varies with behavioral state. J. Neurosci., 2001, 21(5), 1656-1662.
82. Zeitzer, J. M.; Buckmaster, C. L.; Lyons, D. M.; Mignot, E. Increasing length of wakefulness and modulation of hypocretin-1 in the wake-consolidated squirrel monkey. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2007, 293(4), R1736-1742.
83. Rasmussen, D. D.; Boldt, B. M.; Wilkinson, C. W.; Yellon, S. M.; Matsumoto, A. M. Daily melatonin administration at middle age suppresses male rat visceral fat, plasma leptin, and plasma insulin to youthful levels. Endocrinology, 1999, 140(2), 1009-1012.
84. Wolden-Hanson, T.; Mitton, D. R.; McCants, R. L.; Yellon, S. M.; Wilkinson, C. W.; Matsumoto, A. M.; Rasmussen, D. D. Daily melatonin administration to middle-Aged male rats suppresses body weight, intraabdominal adiposity, and plasma leptin and insulin independent of food intake and total body fat. Endocrinology, 2000, 141(2), 487-497.
85. Kitagawa, A.; Ohta, Y.; Ohashi, K. Melatonin improves metabolic syndrome induced by high fructose intake in rats. J. Pineal. Res., 2012, 52(4), 403-413.
86. Picinato, M. C.; Haber, E. P.; Cipolla-Neto, J.; Curi, R.; de Oliveira Carvalho, C. R.; Carpinelli, A. R. Melatonin inhibits insulin secretion and decreases PKA levels without interfering with glucose metabolism in rat pancreatic islets. J. Pineal. Res., 2002, 33(3), 156-160.
87. Peschke, E. Melatonin, endocrine pancreas and diabetes. J. Pineal. Res., 2008, 44(1), 26-40.
88. Tan, D. X.; Manchester, L. C.; Fuentes-Broto, L.; Paredes, S. D.; Reiter, R. J. Significance and application of melatonin in the regulation of brown adipose tissue metabolism: relation to human obesity. Obes. Rev., 2011, 12(3), 167-188.
89. Bahadoran, Z.; Golzarand, M.; Mirmiran, P.; Shiva, N.; Azizi, F. Dietary total antioxidant capacity and the occurrence of metabolic syndrome and its components after a 3-year follow-up in adults: Tehran Lipid and Glucose Study. Nutr. Metab. (Lond.), 2012, 9(1), 70.
90. Volkow, N. D.; Wang, G. J.; Fowler, J. S.; Tomasi, D.; Baler, R. Food and drug reward: overlapping circuits in human obesity and addiction. Curr. Top. Behav. Neurosci., 2012, 11, 1-24.
91. Opland, D. M.; Leinninger, G. M.; Myers, M. G., Jr. Modulation of the mesolimbic dopamine system by leptin. Brain Res., 2010, 1350, 65-70.
92. Figlewicz, D. P.; Evans, S. B.; Murphy, J.; Hoen, M.; Baskin, D. G. Expression of receptors for insulin and leptin in the ventral tegmental area/substantia nigra (VTA/SN) of the rat. Brain Res., 2003, 964(1), 107-115.
93. Leshan, R. L.; Opland, D. M.; Louis, G. W.; Leinninger, G. M.; Patterson, C. M.; Rhodes, C. J.; Munzberg, H.; Myers, M. G., Jr. Ventral tegmental area leptin receptor neurons specifically project to and regulate cocaine-and amphetamine-regulated transcript neurons of the extended central amygdala. J. Neurosci., 2010, 30(16), 5713-5723.
94. Figlewicz, D. P.; Bennett, J. L.; Aliakbari, S.; Zavosh, A.; Sipols, A. J. Insulin acts at different CNS sites to decrease acute sucrose intake and sucrose self-Administration in rats. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2008, 295(2), R388-394.
95. Fadel, J.; Deutch, A. Y. Anatomical substrates of orexin-dopamine interactions: lateral hypothalamic projections to the ventral tegmental area. Neuroscience, 2002, 111(2), 379-387.
96. Davis, J. F.; Tracy, A. L.; Schurdak, J. D.; Tschop, M. H.; Lipton, J. W.; Clegg, D. J.; Benoit, S. C. Exposure to elevated levels of dietary fat attenuates psychostimulant reward and mesolimbic dopamine turnover in the rat. Behav. Neurosci., 2008, 122(6), 1257-1263.
97. Wellman, P. J.; Nation, J. R.; Davis, K. W. Impairment of acquisition of cocaine self-Administration in rats maintained on a high-fat diet. Pharmacol. Biochem. Behav., 2007, 88(1), 89-93.
98. Kim, K. S.; Yoon, Y. R.; Lee, H. J.; Yoon, S.; Kim, S. Y.; Shin, S. W.; An, J. J.; Kim, M. S.; Choi, S. Y.; Sun, W.; Baik, J. H. Enhanced hypothalamic leptin signaling in mice lacking dopamine D2 receptors. J. Biol. Chem., 2010, 285(12), 8905-8917.
99. Alvaro, J. D.; Tatro, J. B.; Duman, R. S. Melanocortins and opiate addiction. Life Sci., 1997, 61(1), 1-9.
100. Benwell, M. E.; Balfour, D. J.; Anderson, J. M. Evidence that tobacco smoking increases the density of (-)-[3H]nicotine binding sites in human brain. J. Neurochem., 1988, 50(4), 1243-1247.
101. Eichenbaum, H. Remembering: functional organization of the declarative memory system. Curr. Biol., 2006, 16(16), R643-645.
102. Squire, L. R. Memory systems of the brain: a brief history and current perspective. Neurobiol. Learn Mem., 2004, 82(3), 171-177.
103. Palovcik, R. A.; Phillips, M. I.; Kappy, M. S.; Raizada, M. K. Insulin inhibits pyramidal neurons in hippocampal slices. Brain Res., 1984, 309(1), 187-191.
104. Benoit, S. C.; Clegg, D. J.; Seeley, R. J.; Woods, S. C. Insulin and leptin as adiposity signals. Recent Prog. Horm. Res., 2004, 59, 267-285.
105. Stice, E.; Spoor, S.; Bohon, C.; Veldhuizen, M. G.; Small, D. M. Relation of reward from food intake and anticipated food intake to obesity: a functional magnetic resonance imaging study. J. Abnorm. Psychol., 2008, 117(4), 924-935.
106. Kenny, P. J. Reward mechanisms in obesity: new insights and future directions. Neuron, 2011, 69(4), 664-679.
107. Ziauddeen, H.; Farooqi, I. S.; Fletcher, P. C. Obesity and the brain: how convincing is the addiction model? Nat. Rev. Neurosci., 2012, 13(4), 279-286.
108. Wallner-Liebmann, S.; Koschutnig, K.; Reishofer, G.; Sorantin, E.; Blaschitz, B.; Kruschitz, R.; Unterrainer, H. F.; Gasser, R.; Freytag, F.; Bauer-Denk, C.; Schienle, A.; Schafer, A.; Mangge, H. Insulin and hippocampus activation in response to images of high-calorie food in normal weight and obese adolescents. Obesity (Silver Spring), 2010, 18(8), 1552-1557.
109. Nakamura, A.; Kawakami, K.; Kametani, F.; Nakamoto, H.; Goto, S. Biological significance of protein modifications in aging and calorie restriction. Ann. N. Y. Acad. Sci., 2010, 1197, 33-39.
110. Violi, F.; Loffredo, L.; Musella, L.; Marcoccia, A. Should antioxi dant status be considered in interventional trials with antioxidants? Heart, 2004, 90(6), 598-602.
111. Neurauter, G.; Schrocksnadel, K.; Scholl-Burgi, S.; Sperner-Unterweger, B.; Schubert, C.; Ledochowski, M.; Fuchs, D. Chronic immune stimulation correlates with reduced phenylalanine turn over. Curr. Drug. Metab., 2008, 9(7), 622-627.
112. Haroon, E.; Raison, C. L.; Miller, A. H. Psychoneuroimmunology meets neuropsychopharmacology: translational implications of the impact of inflammation on behavior. Neuropsychopharmacology, 2012, 37(1), 137-162.