Metabolic syndrome: A brain disease

Canadian Journal of Physiology and Pharmacology

Volumn 90, Issue 9, 2012, Pages 1171-1183

  Singh, Ram B ^a   Gupta, Siddharth ^a   Dherange, Parinita ^a   de Meester, Fabien ^a   Wilczynska, Agnieszka ^a   Alam, Shaan E ^b   Pella, Daniel ^c   Wilson, Douglas W ^d  

^a The Tsim Tsoum Institute   (Poland)

^b UNIVERSITY COLLEGE OF MEDICAL SCIENCES   (India)

^c P J AFÁRIK UNIVERSITY   (Slovakia)

^d DURHAM UNIVERSITY   (United Kingdom)

Author keywords

3 fatty acids; Brain development; Brain disease; Brain heart connection; Diet; Glucose intolerance; Hypothalamus; Insulin resistance; Mediterranean diet; Nutrition

Indexed keywords

ACETYLCHOLINE; CATECHOLAMINE; HYDROCORTISONE; INSULIN; INSULIN RECEPTOR; INTERLEUKIN 10; INTERLEUKIN 4; NEUROPEPTIDE Y; OMEGA 3 FATTY ACID; OMEGA 6 FATTY ACID; POLYUNSATURATED FATTY ACID; PROOPIOMELANOCORTIN; SEROTONIN;

ARCUATE NUCLEUS; BRAIN DEVELOPMENT; BRAIN DISEASE; BRAIN PROTECTION; CHILD NUTRITION; CYTOKINE RELEASE; DIABETES MELLITUS; FOOD INTAKE; HIPPOCAMPUS; HUMAN; INFLAMMATION; MENTAL STRESS; METABOLIC SYNDROME X; NERVE CELL; NONHUMAN; OXIDATIVE STRESS; PARASYMPATHETIC TONE; PERINATAL PERIOD; PRIORITY JOURNAL; REVIEW; SEDENTARY LIFESTYLE; SYMPATHETIC TONE;

AGING; APPETITE REGULATION; ARCUATE NUCLEUS; BRAIN; BRAIN DISEASES; CYTOKINES; FATTY ACIDS, OMEGA-3; FEEDING BEHAVIOR; HUMANS; LIVER; METABOLIC SYNDROME X; RECEPTOR, INSULIN; RISK FACTORS;

EID: 84865417471     PISSN: 00084212     EISSN: 12057541     Source Type: Journal    
DOI: 10.1139/Y2012-122     Document Type: Review

References (85)

1. Abbott, M.-A., Wells, D.G., and Fallon, J.R. 1999. The insulin receptor tyrosine kinase substrate p58/53 and the insulin receptor components of CNS synapses. J. Neurosci. 19(17): 7300-7308. PMID:10460236.
2. Achike, F.I., To, N.-H.P., Wang, H., and Kwan, C.-Y. 2011. Obesity, metabolic syndrome, adipocytes and vascular function: A holistic viewpoint. Clin. Exp. Pharmacol. Physiol. 38(1): 1-10. doi:10. 1111/j.1440-1681.2010.05460.x. PMID:21083697.
3. Agrawal, R., and Gomez-Pinilla, F. 2012. Metabolic syndrome" in the brain: Deficiency in omega-3-fatty acid exacerbates dysfunctions in insulin receptor signaling and cognition. J. Physiol. 590(10): 2485-2499. doi:10.1113/jphysiol.2012.230078. PMID:22473784.
4. Barinaga, M. 1998. No new -neurons dogma loses ground. Science, 279(5359): 2041-2042. doi:10.1126/science.279.5359.2041. PMID:9537913.
5. Barker, D.J., Hales, C.N., Fall, C.H., Osmond, C, Phipps, K., and Clark, P.M.S. 1993. Type 2(non-insulin dependent) diabetes mellitus, hypertension and hyperlipidemia (syndrome X): relation to reduced fetal growth. Diabetologia, 36(1): 62-67. doi:10.1007/ BF00399095. PMID:8436255.
6. Baur, L.A., O'Connor, J., Pan, D.A., Kriketos, A.D., and Storlien, L.H. 1998. The fatty acid composition of skeletal muscle membrane phospholipid: its relationship with the type of feeding and plasma glucose levels in young children. Metabolism, 47(1): 106-112. doi:10.1016/S0026-0495(98)90202-5. PMID:9440487.
7. Beaglehole, R., Bonita, R., Alleyne, G., Horton, R., Li, L., Lincoln, P., et al. Lancet NCD Action Group. 2011. UN High-Level Meeting on Non-Communicable Diseases: addressing four questions. Lancet, 378(9789): 449-455. doi:10.1016/S0140-6736(11) 60879-9. PMID:21665266.
8. Bhatia, H.S., Agrawal, R., Sharma, S., Huo, Y.-X., Ying, Z., and Gomez-Pinilla, F 2011. Omega-3 fatty acid deficiency during brain maturation reduces neuronal and behavioral plasticity in Adulthood. PLoS ONE, 6(12): e28451. doi:10.1371/journal.pone. 0028451. PMID:22163304.
9. Bhopal, R. 2002. Epidemic of cardiovascular disease in south Asians. BMJ, 324(7338): 625-626. doi:10.1136/bmj.324.7338.625. PMID:11895809.
10. Borovikova, L.V., Ivanova, S., Zhang, M., Yang, H., Botchkina, G.I., Watkins, L.R., et al. 2000. Vagal nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature, 405(6785): 458-462. doi:10.1038/35013070. PMID:10839541.
11. Brüning, J.C., Gautam, D., Burks, D.J., Gillette, J., Schubert, M., Orban, P.C., et al. 2000. Role of brain insulin receptor in control of body weight and reproduction. Science, 289(5487): 2122-2125. doi:10.1126/science.289.5487.2122. PMID:11000114.
12. Casas-Agustench, P., López-Uriarte, P., Bulló, M., Ros, E., Cabré-Vila, J J., and Salas-Salvadó, J. 2011. Effects of one serving of mixed nuts on serum lipids, insulin resistance and inflammatory markers in patients with the metabolic syndrome. Nutr. Metab. Cardiovasc. Dis. 21(2): 126-135. doi:10.1016/j.numecd.2009.08. 005. PMID:20031380.
13. Cone, R.D., Cowley, M.A., Butler, A.A., Fan, W., Marks, D.L., and Low, M.J. 2001. The arcuate nucleus as a conduit for diverse signals relevant to energy homeostasis. Int. J. Obes. Relat. Metab. Disord. 25(Suppl. 5): S63-S67. doi:10.1038/sj.ijo.0801913. PMID:11840218.
14. Cunnane, S.C., Francescutti, V., Brenna, T., and Crawford, M.A. 2000. Breast-fed infants achieve a higher rate of brain and whole body docosahexaenoate accumulation than formula fed-infants not consuming dietary docosahexaenoate. Lipids, 35(1): 105-111. doi:10.1007/s11745-000-0501-6. PMID:10695931.
15. Dickson, S.L., Egecioglu, E., Landgren, S., Skibicka, K.P, Engel, J.A., and Jerlhag, E. 2011. The role of the central ghrelin system in reward from food and chemical drugs. Mol. Cell. Endocrinol. 340(1): 80-87. doi:10.1016/j.mce.2011.02.017. PMID:21354264.
16. Dourmap, N, Clero, E., and Costentin, J. 1997. Involvement of cholynergic neurons in the release of dopamine elicited by stimulation mu-opioid receptors in striatum. Brain Res. 749(2): 295-300. doi:10.1016/S0006-8993(96)01319-4. PMID:9138730.
17. Dubnov, G., Pella, D., and Singh, R.B. 2008. The effect of an alpha-linolenic acid rich diet on the circadian rhythm of cardiac events. World Heart J. 1: 49-56.
18. Floto, R.A., and Smith, K.G.C. 2003. The vagus nerve, macrophages and nicotine. Lancet, 361(9363): 1069-1070. doi:10.1016/S0140-6736(03)12902-9. PMID:12672307.
19. Forsyth, J.S., Willatts, P., Agostoni, C., Bissenden, J., Casaer, P., and Boechm, G. 2003. Long chain polyunsaturated fatty acid supplementation in infant formula and blood pressure in later childhood: follow up of a randomized, controlled trial. BMJ, 326 (7396): 953-955. doi:10.1136/bmj.326.7396.953. PMID: 12727766.
20. Furukawa, S., Fujita, T., Shimabukuro, M., Iwaki, M., Yamada, Y., Nakajima, Y., et al. 2004. Increased oxidative stress in obesity and its impact on metabolic syndrome. J. Clin. Invest. 114(12): 1752-1761. PMID:15599400.
21. Hajnal, A., Pothos, E.N., Lenard, L., and Hoebel, B.G. 1998. Effects of feeding and insulin on extracellular acetylcholine in the amygdala of freely moving rats. Brain Res. 785(1): 41-48. doi:10.1016/S0006-8993(97)01291-2. PMID:9526040.
22. Halberg, F., Cornélissen, G., Otsuka, K., Siegelova, J., Fišer, B., Dušek, J., Homolka, J., Salvador, S., Peña, D.L., and Singh, R.B. the BIOCOS project. 2008. Extended consensus on need and means to detect vascular variability disorders (vvds) and vascular variability syndromes (vvss). Intl. J. of Geronto-Geriatrics. 11: 119-146.
23. Halberg, F., Cornélissen, G., Otsuka, K., Siegelova, J., Fišer, B., Dušek, J., Homolka, P., Sánchez de la Peña, S., and Singh, R.B. and the BIOCOS project. 2011. Extended consensus on need and means to detect vascular variability disorders (VVDs) and vascular variability syndromes (VVSs). World Heart J.2(4): 279-306.
24. He, K., Liu, K., Daviglus, M.L., Morris, S.J., Loria, C.M., Van Horn, L., et al. 2006. Magnesium Intake and Incidence of Metabolic Syndrome Among Young Adults. Circulation, 113(13): 1675-1682. doi:10.1161/CIRCULATIONAHA.105.588327. PMID: 16567569.
25. Heine, R.J., Balkau, B., Ceriello, A., Del Prato, S., Horton, E.S., and Taskinen, M.R. 2004. What does postprandial hyperglycaemia mean? Diabet. Med. 21(3): 208-213. doi:10.1111/j.1464-5491. 2004.01149.x. PMID:15008828.
26. Hori, T., Katafuchi, T., Take, S., and Shimizu, N. 1998. Neuroim-munomodulatory actions of hypothalamic interferon-alpha. Neu-roimmunomodulation, 5(3-4): 172-177. doi:10.1159/000026334. PMID:9730683.
27. Hotamisligil, G.S. 1999. The role of TNF-alpha and TNF receptors in obesity and insulin resistance. J. Intern. Med. 245(6): 621-625. doi:10.1046/j.1365-2796.1999.00490.x. PMID:10395191.
28. Hu, F.B., van Dam, R.M., and Liu, S. 2001. Diet and risk of type 2 diabetes: the role of types of fat and carbohydrate. Diabetologia, 44(7): 805-817. doi:10.1007/s001250100547. PMID:11508264.
29. Innis, S.M. 2004. Polyunsaturated fatty acids in human milk: an essential role in infant development. Adv. Exp. Med. Biol. 554: 27-43. PMID:15384565.
30. Jobst, E.E., Enriori, P.J., and Cowley, M.A. 2004. The electro-physiology of feeding circuits. Trends Endocrinol. Metab. 15(10): 488-499. doi:10.1016/j.tem.2004.10.007. PMID:15541648.
31. Joint WHO/FAO Expert Consultation. 2003. Diet, Nutrition and the Prevention of Chronic Diseases. WHO Technical Report Series, 916. WHO, Geneva, Switzerland.
32. Jovinge, S., Hamsten, A., Tornvall, P., Proudler, A., Båvenholm, P., Ericsson, C.-G., et al. 1998. Evidence for a role of tumor necrosis factor alpha in disturbances of triglyceride and glucose metabolism predisposing to coronary heart disease. Metabolism, 47(1): 113-118. doi:10.1016/S0026-0495(98)90203-7. PMID:9440488.
33. Koletzo, B., Agostoni, C., Carlson, S.E., Clandinin, T., Hornstra, G., Neuringer, M., et al. 2001. Long chain polyunsaturated fatty acids (LC-PUFAs) and perinatal development. Acta Paediatr. 90(4): 460-464. doi:10.1111/j.1651-2227.2001.tb00452.x. PMID: 11332943.
34. Kumar, G.S., Das, U.N., Kumar, K.V., Madhavi, N., Das, N.P., and Tan, B.K.H. 1992. Effects of n-6 and n-3 fatty acids on the proliferation of human lymphocytes and their secretion of TNF-a and IL-2 by human in vitro. Nutr. Res. 12(7): 815-820. doi:10. 1016/S0271-5317(05)80639-6.
35. Lauritzen, I., Blondeau, N., Heurteaux, C., Widmann, C., Romey, G., and Lazdunski, M. 2000. Polyunsaturated fatty acids are potent neuroprotectors. EMBO J. 19(8): 1784-1793. doi:10.1093/emboj/ 19.8.1784. PMID:10775263.
36. Lawrence, J.M., Stirling, C., Reid, J., Reckless, J.P.D., and Taylor, G.J. 2004. Favorable effects of pioglitazones and metformin compared with gliclazide on lipoprotein subfractions in overweight patients with early type 2 diabetes. Diab. Care, 27: 41-46.
37. Liese, A.D., Roach, A.K., Sparks, K.C., Marquart, L., D'Agostino, R. B., and Mayer-Davis, E.J. 2003. Whole grain intake and insulin sensitivity: the insulin resistance Atherosclerosis Study. Am. J. Clin. Nutr. 78(5): 965-971. PMID:14594783.
38. Mattson, M.P., and Camandola, S. 2001. NF-kB in neuronal plasticity and neurodegenerative disorders. J. Clin. Invest. 107(3): 247-254. doi:10.1172/JCI11916. PMID:11160145.
39. McKeown, N.M., Meigs, J.B., Liu, S., Saltzman, E., Wilson, P.W.F., and Jacques, P. 2004. Carbohydrate nutrition, insulin resistance and the prevalence of metabolic syndrome in the Framingham Offspring cohort. Diabetes Care, 27(2): 538-546. doi:10.2337/ diacare.27.2.538. PMID:14747241.
40. McNay, D.E.G., Briancon, N., Kokoeva, M.V., Maratos Flier, E., and Flier, J.S. 2012. Remodeling of the arcuate nucleus energy-balance circuit is inhibited in obese mice. J. Clin. Invest. 122(1): 142-152. doi:10.1172/JCI43134. PMID:22201680.
41. Mechirova, V., Singh, R.B., De Meester, F., Juneja, L., and Pella, D. 2009. Protective effects of wild food whole grains against cardiovascular disease? World Heart J. 1: 137-138.
42. Minami, M., Kimura, S., Endo, T., Hamaue, N., Hirafuji, M., Togashi, H., et al. 1997. Dietary docosahexaenoic acid increases cerebral acetylcholine levels and improves passive avoidance-performance in stroke-prone spontaneously hypertensive rats. Pharmacol. Biochem. Behav. 58(4): 1123-1129. doi:10.1016/ S0091-3057(97)00300-6. PMID:9408223.
43. Möhlig, M., Boeing, H., Spranger, J., Osterhoff, M., Kroke, A., Fisher, E., et al. 2004. Body mass index and C-174G interleukin-6 promoter polymorphism interact in predicting type 2 diabetes. J. Clin. Endocrinol. Metab. 89(4): 1885-1890. doi:10.1210/jc.2003-031101. PMID:15070960.
44. Nilsson, L., Sara, V.R., and Nordberg, A. 1988. Insulin like growth factor-1 stimulates the release of acetylcholine from rat cortical slices. Neurosci. Lett. 88(2): 221-226. doi:10.1016/0304-3940(88) 90130-9. PMID:3380358.
45. Nobukata, H., Ishikawa, T., Obata, M., and Shibutani, Y. 2000. Long term administration of highly purified eicosapentaenoic acid ethyl ester prevents diabetes and abnormalities of blood coagulation in maleWBN/kob rats. Metabolism, 49(7): 912-919. doi:10.1053/ meta.2000.6739. PMID:10910004.
46. Ohtani, N., Ohta, M., and Sugano, T. 1997. Microdialysis study of modification of hypothalamic neurotransmitters in streptozotocin-diabetic rats. J. Neurochem. 69(4): 1622-1628. doi:10.1046/j. 1471-4159.1997.69041622.x. PMID:9326291.
47. Pella, D., Thomas, N., Tomlinson, B., and Singh, R.B. 2003. Prevention of coronary artery disease: the south Asian paradox. Lancet, 361(9351): 79. doi:10.1016/S0140-6736(03)12139-3. PMID:12517494.
48. Pella, D., Singh, R.B., Otsuka, K., Chiang, C.E., and Joshi, S.R. 2004. Nutritional predictors and modulators of metabolic syndrome. J. Nutr. Environ. Med. 14(1): 3-16. doi:10.1080/ 13590840410001695220.
49. Pella, D., Otsuka, K., and Singh, R.B. 2011. Metabolic syndrome: A disease of the brain. The Open Nutra J. 4(1): 107-118. doi:10. 2174/1876396001104010107.
50. Perez Tilve, D., Hofmann, S.M., Basford, J., Nogueiras, R., Pfluger, P.T., Patterson, J.T., et al. 2010. Melanocortin signaling in the CNS directly regulates circulating cholesterol. Nat. Neurosci. 13(7): 877-882. [Volume.] doi:10.1038/nn.2569. PMID:20526334.
51. Poppitt, S.D., Strik, C.M., MacGibbon, A.K., McArdle, B.H., Budgett, S.C., and McGill, A.T. 2010. Fatty acid chain length, postprandial satiety and food intake in lean men. Physiol. Behav. 101(1): 161-167. doi:10.1016/j.physbeh.2010.04.036. PMID:20451538.
52. Ragozzino, M.E., Unick, K.E., and Gold, P.E. 1996. Hippocampal acetylcholine release during memory testing in rats: augmentation by glucose. Proc. Natl. Acad. Sci. U.S.A. 93(10): 4693-4698. doi:10.1073/pnas.93.10.4693. PMID:8643466.
53. Ravelli, A.C., van der Meulen, J.H., Osmond, C., Barker, D.J., and Bleker, O.P. 2000. Infant feeding and adult glucose tolerance, lipid profile, blood pressure and obesity. Arch. Dis. Child. 82(3): 248-252. doi:10.1136/adc.82.3.248. PMID:10685933.
54. Rumawas, M.E., Meigs, J.B., Dwyer, J.T., McKeown, N.M., and Jacques, P.F. 2009. Mediterranean-style dietary pattern, reduced risk of metabolic syndrome traits, and incidence in the Framing-ham Offspring Cohort. Am. J. Clin. Nutr. 90(6): 1608-1614. doi:10.3945/ajcn.2009.27908. PMID:19828705.
55. Sahu, A., Dube, M.G., Phelps, C.P., Sninsky, C.A., Kalra, P.S., and Kalra, S.P. 1995. Insulin and insulin like growth factor II suppress neuropeptide Y release from the nerve terminals in the paraventricular nucleus: a putative hypothalamic site for energy homeostasis. Endocrinology, 136(12): 5718-5724. doi:10.1210/ en.136.12.5718. PMID:7588328.
56. Salem, N., Wegher, B., Mena, P., and Uauy, R. 1996. Arachidonic and docosahaexaenoic acids are biosynthesized from their 18-carbon precursors in human infants. Proc. Natl. Acad. Sci. U.S.A. 93(1): 49-54. doi:10.1073/pnas.93.1.49. PMID:8552667.
57. Salmerón, J., Hu, F.B., Manson, J.E., Stampfer, M.J., Colditz, G.A., Rimm, E.B., and Willett, W.C. 2001. Dietary fat intake and risk of type 2 diabetes in women. Am. J. Clin. Nutr. 73(6): 1019-1026. PMID:11382654.
58. Sawada, T., and Yokoi, K. 2010. Effect of zinc supplementation on mood states in young women: a pilot study. Eur. J. Clin. Nutr. 64 (3): 331-333. doi:10.1038/ejcn.2009.158. PMID:20087376.
59. Schulze, M.B., and Hu, F.B. 2004. Dietary approaches to prevent the metabolic syndrome. Quality versus quantity of carbohydrates. Diabetes Care, 27(2): 613-614. doi:10.2337/diacare.27.2.613. PMID:14747248.
60. Schwartz, M.W., and Porte, D. 2005. Diabetes, Obesity and the Brain. Science, 307(5708): 375-379. doi:10.1126/science. 1104344. PMID:15662002.
61. Simopoulos, A.P. 2002. Genetic variation and dietary response: nutrigenetics/ nutrigenomics. Asia Pac. J. Clin. Nutr. 11(s6): S117-S128. doi:10.1046/j.1440-6047.11.s6.3.x.
62. Simopoulos, A.P. 2003. Importance of the ratio of omega-6/omega-3 essential fatty acids: evolutionary aspects. World Rev. Nutr. Diet. 92: 1-22. doi:10.1159/000073788. PMID:14579680.
63. Simopoulos, A.P., and Pavlow, K.N. (Editors). 2001. Nutrition and Fitness: diet, genes, physical activity and health. In Proceedings of the 4th International Conference on Nutrition and Fitness. Athens, World Review of Nutrition and Dietetics, Vol. 89.
64. Singh, R.B., Rastogi, S.S., Rastogi, V., Niaz, M.A., Madhu, S.V., Chen, M., and Shoumin, Z. 1997a. Blood pressure trends, plasma insulin levels, and risk factors in rural and urban elderly populations of North India. Coron. Artery Dis. 8(7): 463-468. doi:10.1097/00019501-199707000-00009. PMID:9383608.
65. Singh, R.B., Niaz, M.A., Sharma, I.P., Kumar, R., Rastogi, V., and Moshiri, M. 1997b. Randomized, double blind, placebo controlled trial of fish oil and mustard oil in patients with suspected acute myocardial infarction. The Indian experiment of infarct survival. Cardiovasc. Drugs Ther. 11(3): 485-491. doi:10.1023/ A:1007757724505. PMID:9310278.
66. Singh, R.B., Beegom, R., Mehta, A.S., Niaz, M.A., De, A.K., Mitra, R.K., et al. 1999. Social class, coronary risk factors and undernutrition, a double burden of diseases, in women during transition, in five Indian cities. Int. J. Cardiol. 69(2): 139-147. PMID:10549837.
67. Singh, R.B., Tomlinson, B., Thomas, N., and Sharma, R. 2001a. Coronary artery disease and coronary risk factors: the South Asian paradox. J. Nutr. Environ. Med. 11(1): 43-51. doi:10.1080/ 13590840020030258.
68. Singh, R. B., Dubnov, G., Niaz, M.A., Ghosh, S., Singh, R., Rastogi, S.S., et al. 2002. The effect of an Indo Mediterranean diet on progression of coronary artery disease in high risk patients: the Indo-Mediterranean diet heart study. Lancet, 360(9344): 1455-1461. doi:10.1016/S0140-6736(02)11472-3. PMID:12433513.
69. Singh, R.B., Pella, D., Mechirova, V., and Otsuka, K. 2004. Can brain dysfunction be a predisposing factor in metabolic syndrome? Biomed. Pharmacother. 58(Suppl. 1): S56-S68. doi:10.1016/ S0753-3322(04)80011-8. PMID:15754841.
70. Singh, R.B., Vargova, V., Mechirova, V., and Pella, D. 2009a. Acute Coronary Syndrome: A Progression of Pre-Metabolic Syndrome. World Heart J. 1: 307-308.
71. Singh, R.B., De Meester, F., Pella, D., Basu, T.K., and Watson, R. 2009b. Globalization of Dietary Wild Foods Protect against Cardiovascular Disease and all Cause Mortalities? A Scientific Statement from the International College of Cardiology, Columbus Paradigm Institute and the International College of Nutrition. The Open Nutraceuticals Journal, 2(1): 42-45. doi:10.2174/ 1876396000902010042.
72. Singh, R.B., Cornelissen, G., Kumar, A., Bathina, S., and Halberg, F. 2009c. Larger Circadian Amplitude of Heart Rate Associated with Active Prayer in Hindu Indians in Asia. World Heart J. 1: 219-222.
73. Sternson, S.M., Shepherd, G.M.G., and Friedman, J.M. 2005. Topographic mapping of VMH → arcuate nucleus microcircuits and their reorganization by fasting. Nat. Neurosci. 8(10): 1356-1363. doi:10.1038/nn1550. PMID:16172601.
74. Strik, C.M., Lithander, F.E., McGill, A.T., MacGibbon, A.K., McArdle, B.H., and Poppitt, S.D. 2010. No evidence of differential effects of SFA, MUFA or PUFA on post-ingestive satiety and energy intake: a randomised trial of fatty acid saturation. Nutr. J. 9(1): 24. doi:10.1186/1475-2891-9-24. PMID: 20492735.
75. Takahashi, A., Ishimaru, H., Ikarashi, Y., and Maruyama, Y. 1994. Aspects of hypothalamic neuronal systems in VMH lesion induced obese rats. J. Auton. Nerv. Syst. 48(3): 213-219. doi:10.1016/ 0165-1838(94)90050-7. PMID:7963256.
76. Tanebe, K., Nishijo, H., Muraguchi, A., and Ono, T. 2000. Effects of chronic stress on hypothalamic interleukin-1 beta, interleukin-2, and gonadotrophin-releasing hormone gene expression in ovar-ectomized rats. J. Neuroendocrinol. 12(1): 13-21. doi:10.1046/j. 1365-2826.2000.00414.x. PMID:10692139.
77. Thomas, G.N., Tomlinson, B., Chan, J.C.N., Lee, Z.S.K., Cockram, C.S., and Critchley, J.A.J.H. 2000. An insulin receptor gene polymorphism is associated with diastolic blood pressure in Chinese subjects with components of the metabolic syndrome. Am. J. Hypertens. 13(7): 745-752. doi:10.1016/S0895-7061(00)00265-X. PMID:10933564.
78. van den Top, M., Lee, K., Whyment, A.D., Blanks, A.M., and Spanswick, D. 2004. Orexigen-sensitive NPY/AgRP pacemaker neurons in the hypothalamic arcuate nucleus. Nat. Neurosci. 7(5): 493-494. doi:10.1038/nn1226. PMID:15097991.
79. Varela, L., Vázquez, M.J., Cordido, F., Nogueiras, R., Vidal-Puigs, A., Diéguez, C., and López, M. 2011. Ghrelin and lipid metabolism: key partners in energy balance. J. Mol. Endocrinol. 46(2): R43-R63. PMID:21169422.
80. Venters, H.D., Dantzer, R., and Kelley, K.W. 2000. A new concept in neurodegeneration: TNF-alpha is a silencer of survival signals. Trends Neurosci. 23(4): 175-180. doi:10.1016/S0166-2236(99)01533-7. PMID:10717677.
81. Wan, Q., Xiong, Z.G., Man, H.Y., Ackerley, C.A., Braunton, J., Lu, W.Y., et al. 1997. Recruitment of functional GABA a receptors to postsynaptic domains by insulin. Nature, 388(6643): 686-690. doi:10.1038/41792. PMID:9262404.
82. Wang, H., Yu, M., Ochani, M., Amella, C.A., Tanovic, M., Susarla, S., et al. 2003. Nicotinic acetylcholine receptor alpha-7 subunit is an essential regulator of inflammation. Nature, 421(6921): 384-388. doi:10.1038/nature01339. PMID:12508119.
83. WHO Study Group. 1990. Diet, Nutrition and Prevention of Chronic Diseases, WHO, Geneva, Switzerland. World Health Organization. 2005. WHO, Geneva Non-communicable diseases, WHO, Geneva, Switzerland.
84. Xu, Z., Tong, C., and Eisenach, J.C. 1996. Acetylcholine stimulates the release of nitric oxide from rat spinal cord. Anesthesiology. 85(1): 107-111. doi:10.1097/00000542-199607000-00015. PMID:8694354.
85. Zhou, L., Sutton, G.M., Rochford, J.J., Semple, R.K., Lam, D.D., Oksanen, L.J., et al. 2007. Serotonin 2C receptor agonists improve type 2 diabetes via melanocortin-4 receptor signaling pathways. Cell Metab. 6(5): 398-405. doi:10.1016/j.cmet.2007.10.008. PMID:17983585.