Neural control of the anorexia-cachexia syndrome

American Journal of Physiology - Endocrinology and Metabolism

Volumn 295, Issue 5, 2008, Pages

  Laviano, Alessandro ^a   Inui, Akio ^b   Marks, Daniel L ^c   Meguid, Michael M ^d   Pichard, Claude ^e   Fanelli, Filippo Rossi ^a   Seelaender, Marilia ^f  

^a SAPIENZA UNIVERSITY OF ROME   (Italy)

^b KAGOSHIMA UNIVERSITY   (Japan)

^c OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^d State University of New York Upstate Medical University: College of Medicine   (United States)

^e GENEVA UNIVERSITY HOSPITALS   (Switzerland)

^f UNIVERSITY OF SÃO PAULO   (Brazil)

Author keywords

Cytokines; Malonyl coenzyme A; Melanocortin; Serotonin; Sympathetic output; Vagus nerve

Indexed keywords

COCAINE AND AMPHETAMINE REGULATED TRANSCRIPT PEPTIDE; CYTOKINE; INTERLEUKIN 1; MELANOCORTIN; MESSENGER RNA; NEUROPEPTIDE Y; PROOPIOMELANOCORTIN; SEROTONIN; TUMOR NECROSIS FACTOR ALPHA;

ANOREXIA; AUTONOMIC NERVOUS SYSTEM; CACHEXIA; CATABOLISM; ENERGY EXPENDITURE; FATTY ACID OXIDATION; HEART FAILURE; HOMEOSTASIS; HUMAN; HYPOTHALAMUS; METABOLISM; MORBIDITY; NERVE CELL; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; QUALITY OF LIFE; REVIEW; SEROTONINERGIC SYSTEM; TUMOR GROWTH; VAGUS NERVE; WEIGHT REDUCTION;

ANIMALS; ANOREXIA; CACHEXIA; CYTOKINES; HUMANS; HYPOTHALAMUS; MELANOCORTINS; NERVOUS SYSTEM; SEROTONIN; SYNDROME;

EID: 57049186323     PISSN: 01931849     EISSN: 15221555     Source Type: Journal    
DOI: 10.1152/ajpendo.90252.2008     Document Type: Review

References (94)

1. Balthasar N, Dalgaard LT, Lee CE, Yu J, Funahashi H, Williams T, Ferreira M, Tang V, McGovern RA, Kenny CD, Christiansen LM, Edelstein E, Choi B, Boss O, Aschkenasi C, Zhang CY, Mountjoy K, Kishi T, Elmquist JK, Lowell BB. Divergence of melanocortin pathways in the control of food intake and energy expenditure. Cell 123: 493-505, 2005.
2. Bartsch C, Bartsch H, Fluchter SH, Mecke D, Lippert TH. Diminished pineal function coincides with disturbed circadian endocrine rhythmicity in untreated primary cancer patients. Consequence of premature aging or of tumor growth? Ann NY Acad Sci 719: 502-525, 1994.
3. Bernstein IL. Neural mediation of food aversions and anorexia induced by tumor necrosis factor and tumors. Neurosci Biobehav Rev 20: 177-181, 1996.
4. Blaha V, Yang ZJ, Meguid MM, Chai JK, Oler A, Zadak Z. Ventromedial nucleus of hypothalamis is related to the development of cancer-induced anorexia: in vivo microdialysis study. Acta Medica (Hradec Kralove) 41: 3-11, 1998.
5. Brito MN, Brito NA, Baro DJ, Song CK, Bartness TJ. Differential activation of the sympathetic innervation of adipose tissues by melanocortin receptor stimulation. Endocrinology 148: 5339-5347, 2007.
6. Broekhuizen R, Grimble RF, Howell WM, Shale DJ, Creutzberg EC, Wouters EF, Schols AM. Pulmonary cachexia, systemic inflammation profile, and the interleukin 1beta-511 single nucleotide polymorphism. Am J Clin Nutr 82: 1059-1064, 2005.
7. Brooks SL, Neville AM, Rothwell NJ, Stock MJ, Wilson S. Sympathetic activation of brown-adipose-tissue thermogenesis in cachexia. Biosci Rep 1: 509-517, 1981.
8. Cangiano C, Cascino A, Ceci F, Laviano A, Mulieri M, Muscaritoli M, Rossi-Fanelli F. Plasma and CSF tryptophan in cancer anorexia. J Neural Transm Gen Sect 81: 225-233, 1990.
9. Cha SH, Hu Z, Chohnan S, Lane MD. Inhibition of hypothalamic fatty acid synthase triggers rapid activation of fatty acid oxidation in skeletal muscle. Proc Natl Acad Sci USA 102: 14557-14562, 2005.
10. Cha SH, Rodgers JT, Puigserver P, Chohnan S, Lane MD. Hypothalamic malonyl-CoA triggers mitochondrial biogenesis and oxidative gene expression in skeletal muscle: role of PGC-1alpha. Proc Natl Acad Sci USA 103: 15410-15415, 2006.
11. Chance WT, Xiao C, Dayal R, Sheriff S. Alteration of NPY and Y1 receptor in dorsomedial and ventromedial areas of hypothalamus in anorectic tumor-bearing rats. Peptides 28: 295-301, 2007.
12. Chen C, Jiang W, Tucci F, Tran JA, Fleck BA, Hoare SR, Joppa M, Markison S, Wen J, Sai Y, Johns M, Madan A, Chen T, Chen CW, Marinkovic D, Arellano M, Saunders J, Foster AC. Discovery of 1-{2-[(1S)-(3- dimethylaminopropionyl)amino-2-methylpropyl]-4-methylphenyl}-4-[(2R) -methyl-3-(4-chlorophenyl)-propionyl]piperazine as an orally active antagonist of the melanocortin-4 receptor for the potential treatment of cachexia. J Med Chem 50: 5249-5252, 2007.
13. Chen HY, Trumbauer ME, Chen AS, Weingarth DT, Adams JR, Frazier EG, Shen Z, Marsh DJ, Feighner SD, Guan XM, Ye Z, Nargund RP, Smith RG, Van der Ploeg LH, Howard AD, MacNeil DJ, Qian S. Orexigenic action of peripheral ghrelin is mediated by neuropeptide Y and agouti-related protein. Endocrinology 145: 2607-2612, 2004.
14. Chen WL, Chen GY, Kuo CD. Hypoxemia and autonomic nervous dysfunction in patients with chronic obstructive pulmonary disease. Respir Med 100: 1547-1553, 2006.
15. Cheung W, Pin X, Little BM, Cone RD, Marks DL, Mak RH. Role of leptin and melanocortin signaling in uremia-associated cachexia. J Clin Invest 115: 1659-1665, 2005.
16. Cheung WW, Kuo HJ, Markison S, Chen C, Foster AC, Marks DL, Mak RH. Peripheral administration of the melanocortin-4 receptor antagonist NBI-12i ameliorates uremia-associated cachexia in mice. J Am Soc Nephrol 18: 2517-2524, 2007.
17. Cheung WW, Rosengren S, Boyle DL, Mak RH. Modulation of melanocortin signaling ameliorates uremic cachexia. Kidney Int 74: 180-186, 2008.
18. Cone RD. Anatomy and regulation of the central melanocortin system. Nat Neurosci 8: 571-578, 2005.
19. Date Y, Shimbara T, Koda S, Toshinai K, Ida T, Murakami N, Miyazato M, Kokame K, Ishizuka Y, Ishida Y, Kageyama H, Shioda S, Kangawa K, Nakazato M. Peripheral ghrelin transmits orexigenic signals through the noradrenergic pathway from the hindbrain to the hypothalamus. Cell Metab 4: 323-331, 2006.
20. Deboer MD, Zhu X, Levasseur PR, Inui A, Hu Z, Han G, Mitch WE, Taylor JE, Halem HA, Dong JZ, Datta R, Culler MD, Marks DL. Ghrelin treatment of chronic kidney disease: improvements in lean body mass and cytokine profile. Endocrinology 149: 827-835, 2008.
21. Ferreira AC, Martins E Jr, Afeche SC, Cipolla-Neto J, Costa Rosa LF. The profile of melatonin production in tumour-bearing rats. Life Sci 75: 2291-2302, 2004.
22. Fetissov SO, Harro J, Jaanisk M, Järv A, Podar I, Allik J, Nilsson I, Sakthivel P, Lefvert AK, Hökfelt T. Autoantibodies against neuropeptides are associated with psychological traits in eating disorders. Proc Natl Acad Sci USA 102: 14865-14870, 2005.
23. Freitas JJ, Pompeia C, Miyasaka CK, Curi R. Walker-256 tumor growth causes oxidative stress in rat brain. J Neurochem 77: 655-663, 2001.
24. Gambardella A, Tortoriello R, Pesce L, Tagliamonte MR, Paolisso G, Varricchio M. Intralipid infusion combined with propranolol administration has favourable metabolic effects in elderly malnourished cancer patients. Metabolism 48: 291-297, 1999.
25. Gidron Y, Perry H, Martin G. Does the vagus nerve inform the brain about preclinical tumours and modulate them? Lancet Oncol 6: 245-248, 2005.
26. Guijarro A, Laviano A, Meguid MM. Hypothalamic integration of immune function and metabolism. Prog Brain Res 153: 367-405, 2006.
27. Heisler LK, Cowley A, Tecott LH, Fan W, Low MJ, Smart JL, Rubinstein M, Tatro JB, Marcus JN, Holstege H, Lee CE, Cone RD, Elmquist JK. Activation of central melanocortin pathways by fenfluramine. Science 297: 609-611, 2002.
28. Heisler LK, Jobst EE, Sutton GM, Zhou L, Borok E, Thorton-Jones Z, Liu HY, Zigman JM, Balthasar N, Kishi T, Lee CE, Aschkenasi CJ, Zhang CY, Yu J, Boss O, Mountjoy KG, Clifton PG, Lowell BB, Friedman JM, Horvath T, Butler AA, Elmquist JK, Cowley MA. Serotonin reciprocally regulates melanocortin neurons to modulate food intake. Neuron 51: 239-249, 2006.
29. Hoyer D, Carke DE, Fozard JR, Hartig PR, Martin GR, Mylecharane EJ, Saxena PR, Humphrey PP. International Union of Pharmacology classifications of receptors for 5-hydroxy-tryptamine (serotonin). Pharmacol Rev 46: 157-203, 1994.
30. Hu Z, Cha SH, Chohnan S, Lane MD. Hypothalamic malonyl-CoA as a mediator of feeding behavior. Proc Natl Acad Sci USA 100: 12624-12629, 2003.
31. Hyltander A, Daneryd P, Sandstrom R, Korner U, Lundholm K. Beta-adrenergic activity and resting energy metabolism in weight losing cancer patients. Eur J Cancer 36: 330-334, 2000.
32. Ignar DM, Andrews JL, Jansen M, Eilert MM, Pink HM, Lin P, Sherrill RG, Szewczyk JR, Conway JG. Regulation of TNF-alpha secretion by a specific melanocortin-1 receptor peptide agonist. Peptides 24: 709-716, 2003.
33. Inui A. Cancer anorexia-cachexia syndrome: are neuropeptides the key? Cancer Res 59: 4493-4501, 1999.
34. Jatoi A, Loprinzi CL, Sloan JA, Klee GG, Windschitl AE. Neuropeptide Y, leptin, and cholecystokinin 8 in patients with advanced cancer and anorexia: a North Central Cancer Treatment Group exploratory investigation. Cancer 92: 629-633, 2001.
35. Johnen H, Lin S, Kuffner T, Brown DA, Tsai VW, Bauskin AR, Wu L, Pankhurst G, Jiang L, Junankar S, Hunter M, Fairlie WD, Lee NJ, Enriquez RF, Baldock PA, Corey E, Apple FS, Murakami MM, Lin EJ, Wang C, During MJ, Sainsbury A, Herzog H, Breit SN. Tumor-induced anorexia and weight loss are mediated by the TGF-beta superfamily cytokine MIC-1. Nat Med 13: 1333-1340, 2007.
36. Joppa MA, Gogas KR, Foster AC, Markinson S. Central infusion of the melanocortin receptor antagonist agouti-related peptide [AgRP(83-132)] prevents cachexia-related symptoms induced by radiation and colon-26 tumors in mice. Peptides 28: 636-642, 2007.
37. Kalantar-Zadeh K, Block G, McAllister CJ, Humphreys MH, Kopple JD. Appetite and inflammation, nutrition, anemia, and clinical outcome in hemodialysis patients. Am J Clin Nutr 80: 299-307, 2004.
38. Khan S, Tisdale MJ. Catabolism of adipose tissue by a tumour-produced lipid-mobilising factor. Int J Cancer 80: 444-447, 1999.
39. Kishi T, Aschkenasi CJ, Lee CE, Mountjoy KG, Saper CB, Elmquist JE. Expression of melanocortin 4 receptor mRNA in the central nervous system of the rat. J Comp Neurol 457: 213-235, 2003.
40. Lainscak M, Keber I, Anker SD. Body composition changes in patients with systolic heart failure treated with beta blockers: a pilot study. Int J Cardiol 106: 319-322, 2006.
41. Laviano A, Yang ZJ, Meguid MM, Koseki M, Beverly JL. Hepatic vagus does not mediate IL-1alpha induced anorexia. Neuroreport 6: 1394-1396, 1995.
42. Laviano A, Cangiano C, Preziosa I, Riggio O, Conversano L, Cascino A, Ariemma S, Rossi Fanelli F. Plasma tryptophan levels and anorexia in liver cirrhosis. Int J Eat Disord 21: 181-186, 1997.
43. Laviano A, Gleason JR, Meguid MM, Yang ZJ, Cangiano C, Rossi Fanelli F. Effects of intra-VMN mianserin and IL-1ra on meal number in anorectic tumor-bearing rats. J Investig Med 48: 40-48, 2000.
44. Laviano A, Meguid MM, Rossi Fanelli F. Cancer anorexia: clinical implications, pathogenesis and therapeutic strategies. Lancet Oncol 4: 686-694, 2003.
45. Laviano A, Muscaritoli M, Cascino A, Preziosa I, Inui A, Mantovani G, Rossi-Fanelli F. Branched-chain amino acids: the best compromise to achieve anabolism? Curr Opin Clin Nutr Metab Care 8: 408-414, 2005.
46. Laviano A, Meguid MM, Inui A, Muscaritoli M, Rossi-Fanelli F. Therapy insight: cancer anorexia-cachexia syndrome - when all you can eat is yourself. Nat Clin Pract Oncol 2: 158-165, 2005.
47. Laviano A, Meguid MM, Guijarro A, Muscaritoli M, Cascino A, Preziosa I, Molfino A, Rossi Fanelli F. Antimyopathic effects of carnitine and nicotine. Curr Opin Clin Nutr Metab Care 9: 442-448, 2006.
48. Laviano A, Meguid MM, Preziosa I, Fanelli FR. Oxidative stress and wasting in cancer. Curr Opin Clin Nutr Metab Care 10: 449-456, 2007.
49. López M, Lelliott CJ, Tovar S, Kimber W, Gallego R, Virtue S, Blount M, Vázquez MJ, Finer N, Powles TJ, O'Rahilly S, Saha AK, Diéguez C, Vidal-Puig AJ. Tamoxifen-induced anorexia is associated with fatty acid synthase inhibition in the ventromedial nucleus of the hypothalamus and accumulation of malonyl-CoA. Diabetes 55: 1327-1336, 2006.
50. Lundholm K, Daneryd P, Bosaeus I, Körner U, Lindholm E. Palliative nutritional intervention in addition to cyclooxygenase and erythropoietin treatment for patients with malignant disease: Effects on survival, metabolism, and function. Cancer 100: 1967-1977, 2004.
51. Machado AP, Costa Rosa LF, Seelaender MC. Adipose tissue in Walker 256 tumour-induced cachexia: possible association between decreased leptin concentration and mononuclear cell infiltration. Cell Tissue Res 318: 503-514, 2004.
52. Makarenko IG, Meguid MM, Gatto L, Chen C, Ugrumov MV. Decreased NPY innervation of the hypothalamic nuclei in rats with cancer anorexia. Brain Res 961: 100-108, 2003.
53. Makarenko IG, Meguid MM, Gatto L, Chen C, Ramos EJ, Goncalves CG, Ugrumov MV. Normalization of hypothalamic serotonin (5-HT1B) receptor and NPY in cancer after tumor resection: an immunocytochemical study. Neurosci Lett 383: 322-327, 2005.
54. Malaguarnera M, Risino C, Gargante MP, Oreste G, Barone G, Tomasello AV, Costanzo M, Cannizaro MA. Decrease of serum carnitine levels in patients with or without gastrointestinal cancer cachexia. World J Gastroenterol 12: 4541-4545, 2006.
55. Mantovani G, Macciò A, Lai P, Massa E, Ghiani M, Santona MC. Cytokine involvement in cancer anorexia/cachexia: role of megestrol acetate and medroxyprogesterone acetate on cytokine downregulation and improvement of clinical symptoms. Crit Rev Oncog 9: 99-106, 1998.
56. Mantovani G, Macciò A, Madeddu C, Massa E. Cancer-related cachexia and oxidative stress: beyond current therapeutic options. Expert Rev Anticancer Ther 3: 381-392, 2003.
57. Marín Caro MM, Laviano A, Pichard C. Nutritional intervention and quality of life in adult oncology patients. Clin Nutr 26: 289-301, 2007.
58. Markison S, Foster AC, Chen C, Brookhart GB, Hesse A, Hoare SR, Fleck BA, Brown BI, Marks DL. The regulation of feeding and metabolic rate and the prevention of murine cancer cachexia with a small-molecule melanocortin-4 receptor antagonist. Endocrinology 146: 2766-2773, 2005.
59. Marks DL, Ling N, Cone RD. Role of the melanocortin system in cachexia. Cancer Res 61: 1432-1438, 2001.
60. Marks DL, Butler AA, Turner R, Brookhart G, Cone RD. Differential role of melanocortin receptor subtypes in cachexia. Endocrinology 144: 1513-1523, 2003.
61. McCarthy HD, Crowder RE, Dryden S, Williams G. Megestrol acetate stimulates food and water intake in the rat: effects on regional hypothalamic neuropeptide Y concentrations. Eur J Pharmacol 265: 99-102, 1994.
62. Meguid MM, Fetissov SO, Varma M, Sato T, Zhang L, Laviano A, Rossi-Fanelli F. Hypothalamic dopamine and serotonin in the regulation of food intake. Nutrition 16: 843-857, 2000.
63. Meguid MM, Ramos EJ, Laviano A, Varma M, Sato T, Chen C, Qi Y, Das UN. Tumor anorexia: effects on neuropeptide Y and monoamines in paraventricular nucleus. Peptides 25: 261-266, 2004.
64. Menyhert J, Witmann G, Lechman RM, Keller E, Lipositis Z, Fekete C. Cocaine- and amphetamine-regulated transcript (CART) is colocalized with the orexigenic neuropeptide Y and agouti-related protein and absent from the anorexigenic alpha-melanocyte-stimulating hormone neurons in infundibular nucleus of human hypothalamus. Endocrinology 148: 4276-4281, 2007.
65. Molfino A, Muscaritoli M, Cascino A, Fanfarillo F, Fava A, Bertini G, Citro G, Rossi Fanelli F, Laviano A. Free tryptophan/large neutral amino acids ratios in blood plasma do not predict cerebral spinal fluid tryptophan concentrations in interleukin-1-induced anorexia. Pharmacol Biochem Behav 89: 31-35, 2008.
66. Morley JE, Thomas DR, Wilson WW. Cachexia: pathophysiology and clinical relevance. Am J Clin Nutr 83: 735-743, 2006.
67. Mountjoy KG, Robbins LS, Mortrud MT, Cone RD. The cloning of a family of genes that encode the melanocortin receptors. Science 257: 1248-1251, 1992.
68. Muscaritoli M, Bossola M, Aversa Z, Bellantone R, Rossi Fanelli F. Prevention and treatment of cancer cachexia. Eur J Cancer 42: 31-41, 2006.
69. Nachiappan V, Curtiss D, Corkey BE, Kilpatrick L. Cytokines inhibit fatty acid oxidation in isolated rat hepatocytes: synergy among TNF, IL-6, and IL-1. Shock 1: 123-129, 1994.
70. Nagaya M, Moriya J, Yasamura Y, Uematsu M, Ono F, Shimizu W, Ueno K, Kitakaze M, Miyatake K, Kangawa K. Effects of ghrelin administration on left ventricular function, exercise capacity, and muscle wasting in patients with chronic heart failure. Circulation 110: 3674-3679, 2004.
71. Nagaya N, Itoh T, Murakami S, Oya H, Uematsu M, Miyatake K, Kangawa K. Treatment of cachexia with ghrelin in patients with COPD. Chest 128: 1187-1193, 2005.
72. Nicholson JR, Kohler G, Schaerer F, Senn C, Weyemann P, Hofbauer KG. Peripheral administration of a melanocortin 4-receptor inverse agonist prevents loss of lean body mass in tumor-bearing mice. Peptides 317: 771-777, 2006.
73. Opara EI, Laviano A, Meguid MM, Yang ZJ. Correlation between food intake and CSF IL-1 alpha in anorectic tumor bearing rats. Neuroreport 6: 750-752, 1995.
74. Plata-Salaman CR, Ilyin SE, Gayle D. Brain cytokine mRNAs in anorectic rats bearing prostate adenocarcinoma tumor cells. Am J Physiol Regul Integr Comp Physiol 275: R566-R573, 1998.
75. Ramos EJ, Suzuki S, Meguid MM, Laviano A, Sato T, Chen C, Das U. Changes in hypothalamic neuropeptide Y and monoaminergic system in tumor-bearing rats: pre- and post-tumor resection and at death. Surgery 136: 270-276, 2004.
76. Ramos EJ, Meguid MM, Zhang L, Miyata G, Fetissov SO, Chen C, Suzuki S, Laviano A. Nicotine infusion into rat ventromedial nuclei and effects on monoaminergic system. Neuroreport 15: 2293-2297, 2004.
77. Ranpuria R, Hall M, Chan CT, Unruh M. Heart Rate Variability (HRV) in kidney failure: measurement and consequences of reduced HRV. Nephrol Dial Transplant 23: 444-449, 2008.
78. Ruud J, Blomqvist A. Identification of rat brainstem neuronal structures activated during cancer-induced anorexia. J Comp Neurol 504: 275-286, 2007.
79. Sato T, Laviano A, Meguid MM, Chen C, Rossi-Fanelli F, Hatakeyama K. Involvement of plasma leptin, insulin and free tryptophan in cytokine-induced anorexia. Clin Nutr 22: 139-146, 2003.
80. Scarlett JM, Jobst EE, Enriori PJ, Bowe DD, Batra AK, Grant WF, Cowley MA, Marks DL. Regulation of central melanocortin signalling by interleukin-1 beta. Endocrinology 148: 4217-4225, 2007.
81. Taherzadeh S, Sharma S, Chhajlani V, Gantz I, Rajora N, Demitri MT, Kelly L, Zhao H, Ichiyama T, Catania A, Lipton JM. α-MSH and its receptors in the regulation of tumor necrosis factor-α production by human monocyte/macrophages. Am J Physiol Regul Integr Comp Physiol 276: R1289-R1294, 1999.
82. Tecott LH. Serotonin and the orchestration of energy balance. Cell Metab 6: 352-361, 2007.
83. Tisdale MJ. Cachexia in cancer patients. Nat Rev Cancer 2: 862-871, 2002.
84. Torelli GF, Meguid MM, Moldawer LL, Edwards CK 3rd, Kim HJ, Carter JL, Laviano A, Rossi Fanelli F. Use of recombinant human soluble TNF receptor in anorectic tumor-bearing rats. Am J Physiol Regul Integr Comp Physiol 277: R850-R855, 1999.
85. Ulloa L. The vagus nerve and the nicotinic anti-inflammatory pathway. Nat Rev Drug Discov 4: 673-684, 2005.
86. Wang W, Andersson M, Lonnroth C, Svanberg E, Lundholm K. Prostaglandin E and prostacyclin receptor expression in tumor and host tissues from MCG 101-bearing mice: a model with prostanoid-related cachexia. Int J Cancer 115: 582-590, 2005.
87. Wisse BE, Frayo RS, Schwartz MW, Cummings DE. Reversal of cancer anorexia by blockade of central melanocortin receptors in rats. Endocrinology 142: 3292-3301, 2001.
88. Wisse BE, Ogimoto K, Schwartz MW. Role of interlueikin-1beta (IL-1beta) in regulation of energy homeostasis by melanocortins. Peptides 27: 265-273, 2006.
89. Wolfgang MJ, Kurama T, Dai Y, Suwa A, Asaumi M, Matsumoto S, Cha SH, Shimokawa T, Lane MD. The brain-specific carnitine palmitoyltransferase-1c regulates energy homostasis. Proc Natl Acad Sci USA 103: 7282-7287, 2006.
90. Yang ZJ, Koseki M, Meguid MM, Gleason JR, Debonis D. Synergistic effect of rhTNF-α and rhIL-1α in inducing anorexia in rats. Am J Physiol Regul Integr Comp Physiol 267: R1056-R1064, 1994.
91. Yang ZJ, Blaha V, Meguid MM, Laviano A, Oler A, Zadak Z. Interleukin-1alpha injection into ventromedial hypothalamic nucleus of normal rats depresses food intake and release of dopamine and serotonin. Pharmacol Biochem Behav 62: 61-65, 1999.
92. Zheng H, Patterson LM, Phifer CB, Berthoud HR. Brain stem melanocortinergic modulation of meal size and identification of hypothalamic POMC projections. Am J Physiol Regul Integr Comp Physiol 289: R247-R258, 2005.
93. Zhou L, Sutton GM, Rochford JJ, Semple RK, Lam DD, Oksanen LJ, Thornton-Jones ZD, Clifton PG, Yueh CY, Evans ML, McCrimmon RJ, Elmquist JK, Butler AA, Heisler LK. Serotonin 2C receptor agonists improve type 2 diabetes via melanocortin-4 receptor signalling pathways. Cell Metab 6: 398-405, 2007.
94. Zhu CB, Blakely RD, Hewlett WA. The proinflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha activate serotonin transporter. Neuropsychopharmacology 31: 2121-2131, 2006.