Alterations in the peptidergic regulation of energy balance in the course of aging

Current Protein and Peptide Science

Volumn 12, Issue 4, 2011, Pages 316-324

  Petervari E ^a   Soos S ^a   Szekely M ^a   Balasko M ^a  

^a UNIVERSITY OF PÉCS   (Hungary)

Author keywords

Aging; Anabolic peptides; Body composition; Body temperature; Body weight; Catabolic peptides; Food intake; Metabolic rate

Indexed keywords

ADIPONECTIN; AGOUTI RELATED PROTEIN; ALPHA INTERMEDIN; CHOLECYSTOKININ; COCAINE AND AMPHETAMINE REGULATED TRANSCRIPT PEPTIDE; CORTICOTROPIN RELEASING FACTOR; GASTROINTESTINAL POLYPEPTIDE; GHRELIN; GLUCAGON LIKE PEPTIDE 1; GLUCOSE; INSULIN; LEPTIN; MELANIN CONCENTRATING HORMONE; NEUROPEPTIDE Y; OREXIN; OXYNTOMODULIN; PANCREAS POLYPEPTIDE; PEPTIDE YY; PROOPIOMELANOCORTIN;

AGING; ANOREXIA; ARTICLE; ENERGY BALANCE; ENERGY EXPENDITURE; FOOD INTAKE; HUMAN; METABOLIC RATE; MIDDLE AGED; MUSCLE ATROPHY; NONHUMAN; OBESITY; PEPTIDERGIC NERVOUS SYSTEM; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN SYNTHESIS;

AGING; ANIMALS; ENERGY METABOLISM; HUMANS; PEPTIDES;

ANIMALIA;

EID: 79960001017     PISSN: 13892037     EISSN: 18755550     Source Type: Journal    
DOI: 10.2174/138920311795906709     Document Type: Article

References (106)

1. Palkovits, M. Hypothalamic regulation of food intake. Ideggyogy. Szle./Clin. Neurosci., 2003, 56, 288-302.
2. Szekely, M.; Petervari, E.; Balasko, M. Thermoregulation, energy balance, regulatory peptides: recent developments. Front. Biosci., 2010, 15, 1009-1046.
3. Székely, M.; Szelényi, Z.: Regulation of energy balance by peptides: a review. Curr. Protein Pept. Sci., 2005, 6, 327-353.
4. Xu, A.W.; Kaelin, C.B.; Morton, G.J.; Ogimoto, K.; Stanhope, K.; Graham, J.; Baskin, D.G.; Havel, P.; Schwartz, M.W.; Barsh, G.S. Effects of hypothalamic neurodegeneration on energy balance. PLoS Biol., 2005, 3, 2168-2176.
5. Friedman, J.M.; Halaas, J.L. Leptin and the body weight regulation in mammals. Nature, 1998, 395, 763-770.
6. Sahu, A. Minireview: A hypothalamic role in energy balance with special emphasis on leptin. Endocrinology, 2004, 145, 2613-2620.
7. Scarpace, P.J.; Matheny, M.; Moore, R.L.; Tümer, N. Impaired leptin responsiveness in aged rats. Diabetes, 2000, 49, 431-435.
8. Shek, E.W.; Scarpace, P.J. Resistance to the anorexic and thermogenic effects of centrally administered leptin in obese aged rats. Regul. Pept., 2000, 92, 65-71.
9. Baranowska, B.; Bik, W.; Baranowska-Bik, A.; Wolinska-Witort, E.; Szybinska, A.; Martynska, I.; Chmielowska, M. Neuroendo-crine control of metabolic homeostasis in Polish centenarians. J. Physiol. Pharmacol., 2006, 57, 55-61.
10. Gabriely, I.; Ma, X.H.; Yang, X.M.; Atzmon, G.; Rajala, M.W.; Berg, A.H.; Scherer, P., Rossetti, L.; N. Barzilai, N. Removal of visceral fat prevents insulin resistance and glucose intolerance of aging. An adipokine-mediated process? Diabetes, 2002, 51, 2951-2958.
11. Gabriely, I.; Ma, X.H.; Yang, X.M.; Rossetti, L.; Barzilai, N. Leptin resistance during aging is independent of fat mass. Diabetes, 2002, 51, 1016-1021.
12. Soos, S.; Balasko, M.; Jech-Mihalffy, A.; Szekely, M.; Petervari, E. Anorexic vs. metabolic effects of central leptin infusion in rats of various ages and nutritional states. J. Mol. Neurosci., 2010, 41, 97-104.
13. Zhang, L.; Matheny, M.; Tümer, N.; Scarpace, P.J.;Aged-obese rats exhibit robust responses to melanocortin agonist and antagonist despite leptin resistance Neurobiol. Aging, 2004, 25, 1349-1360.
14. Pétervári, E.; Szabad, Á.O.; Soós, S.; Garami, A.; Székely, M.; Balaskó, M. Central alpha-MSH infusion in rats: disparate anorexic vs. metabolic changes with aging. Regul. Pept., 2011, 166, 105-111.
15. Cone, R.D.; Cowley, M.A.; Butler, A.A.; Fan, W.; Marks, D.L.; Low, M.J. The arcuate nucleus as a conduit for diverse signals relevant to energy homeostasis. Internatl. J. Obes., 2001, 25, S63-S67.
16. Porte, D. Jr., Baskin, D.G.; Schwartz, M.W. Leptin and insulin action in the central nervous system. Nutr. Rev., 2002, 60, S20-S29.
17. Benoit, S.C.; Clegg, D.J.; Seeley, R.J.; Woods, S.C. nsulin and leptin as adiposity signals Rec. Prog. Horm. Res., 2004, 59, 267-285.
18. Fernández-Galaz, C.; Fernández-Agulló, T.; Pérez, C.; Peralta, S.; Arribas, C.; Andrés, A.; Carrascosa, J.M.; Ros, M. Long-term food restriction prevents ageing-associated central leptin resistance in Wistar rats. Diabetologia, 2002, 45, 997-1003.
19. Leckström, A.; Lundquist, I.; Ma, Z.; Westermark, P. Islet amyloid polypeptide and insulin relationship in a longitudinal study of the genetically obese (ob/ob) mouse. Pancreas, 1999, 18, 266-273.
20. South, E.H.; Ritter, R.C. Capsaicin application to central or peripheral vagal fibers attenuates CCK satiety. Peptides, 1988, 9, 601-612.
21. Bi, S.; Chen, J.; Behles, R.R.; Hyun, J.; Kopin, A.S.; Moran, T.H. Differential body weight and feeding responses to high-fat diets in rats and mice lacking cholecystokinin 1 receptors. Am. J. Physiol., 2007, 293, R55-R63.
22. de Lartigue, G.; Dimaline, R.; Varro, A.; Dockray, G.J. Cocaineand amphetamine-regulated transcript: stimulation of expression in rat vagal afferent neurons by cholecystokinin and suppression by ghrelin. J. Neurosci., 2007, 27, 2876-2882.
23. Peters, J.H.; Ritter, R.C.; Simasko, S.M. Leptin and CCK selectively activate vagal afferent neurons innervating the stomach and duodenum. Am. J. Physiol., 2006, 290, R1544-R1549.
24. Cano, V.; Merino, B.; Ezquerra, L.; Somoza, B.; Ruiz-Gayo, M. A cholecystokinin-1 receptor agonist (CCK-8) mediates increased permeability of brain barriers to leptin. Br. J. Pharmacol., 2008, 154, 1009-1015.
25. Szelényi, Z.; Székely, M.; Hummel, Z.; Balaskó, M.; Romanovsky, A.A.; Pétervári, E. Cholecystokinin: possible mediator of fever and hypothermia. Front. Biosci., 2004, 9, 301-308.
26. Gibbs, J.; Young, R.; Smith, G.P. Cholecystokinin decreases food intake in rats. J. Comp. Physiol., 1973, 84, 488-493.
27. Stengel, A.; Taché, Y. Interaction between gastric and upper small intestinal hormones in the regulation of hunger and satiety: ghrelin and cholecystokinin take the central stage. Curr. Protein Pept. Sci., 2010, (present issue)
28. Shiraishi, T. CCK as a central satiety factor: behavioral and electrophysiological evidence. Physiol. Behav., 1990, 48, 879-885.
29. Cheng, C.A.; Geoghegan, J.G.; Lawson, D.C.; Berlangieri, S.U.; Akwari, O.; Pappas, T.N. Central and peripheral effects of CCK receptor antagonists on satiety in dogs. Am. J. Physiol., 1993, 265, G219-223.
30. Chapman, I.M.; MacIntosh, C.G.; Morley, J.E.; Horowitz, M. The anorexia of ageing. Biogerontology, 2002, 3, 67-71.
31. MacIntosh, C.G.; Andrews, J.M.; Jones, K.L.; Wishart, J.M.; Morris, H.A.; Jansen, J.B.M.J.; Morley, J.E.; Horowitz, M.; Chapman, I.M. Effects of age on concentrations of plasma cholecystokinin, glucagon-like peptide 1, and peptide YY and their relation to appetite and pyloric motility. Am. J. Clin. Nutr., 1999, 69, 999-1006.
32. Serra-Prat, M.; Fernández, X.; Burdoy, E.; Mussoll, J.; Casamitjana, R.; Puig-Domingo, M. The role of ghrelin in the energy homeostasis of elderly people: a population-based study. J. Endocrinol. Invest., 2007, 30, 484-490.
33. Akimoto, S.; Miyasaka, K. Age-associated changes of appetiteregulating peptides. Geriatr. Gerontol. Int., 2010, 10, S107-S119.
34. Miyasaka, K.; Kanai, S.; Masuda, M.; Ohta, M.; Kawanami, T.; Matsumoto, M.; Funakoshi, A. Gene expression of cholecystokinin (CCK) and CCK receptors, and its satiety effect in young and old male rats. Arch. Gerontol. Geriatr., 1995, 21, 147-155.
35. Sturm, K.; MacIntosh, C.G.; Parker, B.A.; Wishart, J.; Horowitz, M.; Chapman, I.M. Appetite, food intake, and plasma concentrations of cholecystokinin, ghrelin, and other gastrointestinal hormones in undernourished older women and well-nourished young and older women. J. Clin. Endocr. Metab., 2003, 88, 3747-3755.
36. Cnop, M.; Havel, P.J.; Utzschneider, K.M.; Carr, D.B.; Sinha, M.K.; Boyko, E.J.; Retzlaff, B.M.; Knopp, R.H.; Brunzell, J.D.; Kahn, S.E. Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex. Diabetologia, 2003, 46, 459-469.
37. Qi, Y.; Takahashi, N.; Hileman, S.M.; Patel, H.R.; Berg, A.H.; Pajvani, U.B.; Scherer, P.E.; Ahima, R.S. Adiponectin acts in the brain to decrease body weight. Nat. Med., 2004, 10, 524-529.
38. Lutz, T.A. The role of amylin in the control of energy homeostasis. Am. J. Physiol., 2010, 298, R1475-R1484.
39. Münzberg H.; Huo, L.; Nillni, E.A.; Hollenberg, A.N.; Bjorbaek, C. Role of signal transducer and activator of transcription 3 in regulation of hypothalamic proopiomelanocortin gene expression by leptin. Endocrinology, 2003, 144, 2121-2131.
40. Li, G.; Mobbs, C.V.; Scarpace, P.J. Central pro-opiomelanocortin gene delivery results in hypophagia, reduced visceral adiposity, and improved insulin sensitivity in genetically obese Zucker rats. Diabetes, 2003, 52, 1951-1957
41. Mizuno, T.M.; Kelley, K.A.; Pasinetti, G.M.; Roberts, J.L.; Mobbs, C.V. Transgenic neuronal expression of proopiomelanocortin attenuates hyperphagic response to fasting and reverses metabolic impairments in leptin-deficient obese mice. Diabetes, 2003, 52, 2675-2683.
42. Masuzaki, H.; Tanaka, T.; Ebihara, K.; Hosoda, K.; Nakao, K. Hypothalamic melanocortin signaling and leptin resistance - Perspective of therapeutic application for obesity-diabetes syndrome. Peptides, 2009, 30, 1383-1386.
43. Soos, S.; Petervari, E.; Szekely, M.; Jech-Mihalffy, A.; Balasko, M. Complex catabolic effects of central alpha-MSH infusion in rats of altered nutritional states: differences from leptin. J. Mol. Neurosci., 2011, 43, 209-216.
44. Garza, J.C.; Kim, C.S.; Liu, J.; Zhang, W.; Lu, X-Y. Adenoasociated virus-mediated knockdown of melanocortin-4 receptor in the paraventricular nucleus of the hypothalamus promotes high-fat diet-induced hyperphagia and obesity. J. Endocrinol., 2008, 197, 471-482.
45. Grill, H.J.; Ginsberg, A.B.; Seeley, R.J.; Kaplan, J.M. Brainstem application of melanocortin receptor ligands produces long-lasting effects on feeding and body weight. J. Neurosci., 1998, 18, 10128-10135.
46. Skibicka, K.P.; Grill, H.J. Energetic responses are triggered by caudal brainstem melanocortin receptor stimulation and mediated by local sympathetic effector circuits. Endocrinology, 2008, 149, 3605-3616.
47. Kmiec, Z. Central control of food intake in aging. Interdiscip. Top. Gerontol., 2010, 37, 37-50.
48. Hwa, J.J.; Ghibaudi, L.; Gao, J.; Parker, E.M. Central melanocortin system modulates energy intake and expenditure in obese and lean Zucker rats. Am. J. Physiol., 2001, 281, R444-R451.
49. Li, G.; Zhang, Y.; Wilsey, J.T.; Scarpace, P.J. Hypothalamic proopiomelanocortin gene delivery ameliorates obesity and glucose intolerance in aged rats. Diabetologia, 2005, 48, 2376-2385.
50. Gruenewald, D.A.; Matsumoto, A.M. Age-related decrease in proopiomelanocortin gene expression in the arcuate nucleus of the male rat brain. Neurobiol. Aging, 1991, 12, 113-121.
51. Pétervári, E.; Garami, A.; Soós, S.; Székely, M.; Balaskó, M. Agedependence of alpha-MSH-induced anorexia. Neuropeptides, 2010, 44 315-322.
52. López, M.; Lage, R.; Tung, Y.C.L.; Challis, B.G.; Varela, L.; Virtue, S.; O'Rahilly, S.; Vidal-Puig, A.; Diéguez, C.; Coll, A.P. Orexin expression is regulated by alpha-melanocyte stimulating hormone. J. Neuroendocrinol., 2007, 19, 703-707.
53. Pelleymounter, M.A.; Joppa, M.; Ling, N.; Foster, A.C. Pharmacological evidence supporting a role for central corticotrophinreleasing factor2 receptors in behavioral, but not endocrine, response to environmental stress. J. Pharmacol. Exp. Ther., 2002, 302, 145-152.
54. Currie, P.J.; Coscina, D.V.; Bishop, C.; Coiro, C.D.; Koob, G.F.; Rivier, J.; Vale, W. Hypothalamic paraventricular nucleus injections of urocortin alter food intake and respiratory quotient. Brain Res., 2001, 916, 222-228.
55. Fekete, C.; Legradi, G.; Mihaly, E.; Tatro, J.B.; Rand, W.M.; Lechan, R.M. Alpha-melanocyte stimulating hormone prevents fasting-induced suppression of corticotrophin-releasing hormone gene expression in the rat hypothalamic paraventricular nucleus. Neurosci. Lett., 2000, 289, 152-156.
56. Seeley, R.J.; Matson, C.A.; Chavez, M.; Woods, S.C.; Dallman, M.F.; Schwartz, M.W. Behavioral, endocrine, and hypothalamic responses to involuntary overfeeding. Am. J. Physiol., 1996, 271, R819-R823.
57. Bale, T.L.; Vale, W.W. CRF and CRF receptors: role in stress responsivity and other behaviors. Annu. Rev. Pharmacol. Toxicol., 2004, 44, 525-557.
58. Shibasaki, T.; Yamauchi, N.; Kato, Y.; Masuda, A.; Imaki, T.; Hotta, M.; Demura, H.; Oono, H.; Ling, N.; Shizume, K. Involvement of corticotropin-releasing factor in restraint stress-induced anorexia and reversion of the anorexia by somatostatin in the rat. Life Sci., 1988, 43, 1103-1110.
59. Harris, R.B.S.; Mitchell, T.D.; Simpson, J.; Redmann, S.M., Jr.; Youngblood, B.D.; Ryan, D.H. Weight loss in rats exposed to repeated acute restraint stress is independent of energy or leptin status. Am. J. Physiol., 2002, 282, R77-R88.
60. Pan, W.; Tu, H.; Hsuchou, H.; Daniel, J.; Kastin, A.J. Unexpected amplification of leptin-induced Stat3 signaling by urocortin: implications for obesity. J. Mol. Neurosci., 2007, 33, 232-238.
61. Smagin, G.N.; Howell, L.A.; Redmann, S. Jr.; Ryan, D.H.; Harris, R.B.S. Prevention of stress-induced weight loss by third ventricle CRF receptor antagonist. Am. J. Physiol., 1999, 276, R1461-R1468.
62. Cullen, M.J.; Ling, N.; Foster, A.C.; Pelleymounter, M.A. Urocortin, corticotropin releasing factor-2 receptors and energy balance. Endocrinology, 2001, 142, 992-999.
63. Telegdy, G.; Adamik, A. Involvement of CRH receptors in urocortin- induced hyperthermia. Peptides, 2008, 29, 1937-1942.
64. Kawashima, S.; Sakihara, S.; Kageyama, K.; Nigawara, T.; Suda, T. Corticotropin-releasing factor (CRF) is involved in the acute anorexic effect of alpha-melanocyte-stimulating hormone: a study using CRF deficient mice. Peptides, 2008, 29, 2169-2174.
65. Germano, C.M.; Castro, M.; Rorato, R.; Costa, D.B.; Antunes- Rodrigues, J.; Elias, C.F.; Elias, L.L. Downregulation of melanocortin-4 receptor during refeeding and its modulation by adrenalectomy in rats. Horm. Metab. Res., 2008, 40, 842-847.
66. Okamoto, S.; Kimura, K.; Saito, M. Anorectic effect of leptin is mediated by hypothalamic corticotrophin-releasing hormone, but not by urocortin, in rats. Neurosci. Lett., 2001, 307, 179-182.
67. Bchini-Hooft van Huisduijnen, O.B.; Rohner-Jeanrenaud, F.; Jeanrenaud, J. Hypothalamic neuropeptide Y messenger ribonucleic acid levels in pre-obese and genetically obese (fa/fa) rats; potential regulation thereof by corticotrophin-releasing factor. J. Neuroimmunol., 1993, 5, 381-386.
68. Bao, A.M.; Swaab, D.F. Gender difference in age-related number of corticotrophin-releasing hormone-expressing neurons in the human hypothalamic paraventricular nucleus and the role of sex hormones. Neuroendocrinology, 2007, 85, 27-36.
69. Herman, J.P.; Larson, B.R.; Speert, D.N.; Seasholtz, A.F. Hypothalamo- pituitary-adrenocortical dysregulation in aging F344/Brown-Norway F1 hybrid rats. Neurobiol. Aging, 2001, 22, 323-332.
70. Kaneda, T.; Makino, S.; Nishiyama, M.; Asaba, K.; Hashimoto, K. Differential neuropeptide responses to starvation with ageing. J. Neuroendocrinol., 2001, 13, 1066-1075.
71. Héroux, J.A.; Grigoriadis, D.E.; De Souza, E.B. Age-related decrease in corticotrophin-releasing factor (CRF) receptors in rat brain and anterior pituitary gland. Brain Res., 1991, 542, 155-158.
72. Kasckow, J.W.; Regmi, A.; Mulchahey, J.J.; Plotsky, P.M.; Hauger, R.L. Changes in brain corticotrophin-relesing factor messenger RNA expression in aged Fischer 344 rats. Brain Res., 1999, 822, 228-230.
73. Sohn, E.H.; Wolden-Hanson, T.; Matsumoto, A.M. Testosterone (T)-induced changes in arcuate nucleus cocaine-amphetamineregulated transcript and NPY mRNA are attenuated in old compared to young male brown Norway rats: Contribution of T to agerelated changes in cocaine-amphetamine-regulated transcript and NPY gene expression. Endocrinology, 2002, 143, 954-963.
74. Wolden-Hanson, T.; Marck, B.T.; Matsumoto, A.M. Blunted hypothalamic gene expression in response to fasting, but preservation of feeding responses to AgRP in aging male Brown Norway rats. Am. J. Physiol., 2004, 287, R138-R146.
75. Kappeler, L.; Gourdji, D.; Zizzari, P.; Bluet-Pajot, M.T.; Epelbaum, J. Age-associated changes in hypothalamic and pituitary neuroendocrine gene expression in the rat. J. Neuroendocrinol., 2003, 15, 592-601.
76. Lu, S.; Guan, J.L.; Wang, Q.P.; Uehara, K.; Yamada, S.; Goto, N.; Date, Y.; Nakazato, M.; Kojima, M.; Kangawa, K.; Shioda, S. Immunocytochemical observation of ghrelin-containing neurons in the rat arcuate nucleus. Neurosci. Lett., 2002, 321, 157-160.
77. Toshinai, K.; Mondal, M.S.; Nakazato, M.; Date, Y.; Murakami, N.; Kojima, M.; Kangawa, K.; Matsukura, S. Upregulation of ghrelin expression in the stomach upon fasting, insulin-induced hypoglycemia, and leptin administration. Biochem. Biophys. Res. Commun., 2001, 281, 1220-1225.
78. Olszewski, P.K.; Bomberg, E.M.; Grace, M.K.; Levine, A.S. Alpha- melanocyte stimulating hormone and ghrelin: central interaction in feeding control. Peptides, 2007, 28, 2084-2089.
79. Tschöp, M.; Smiley, D.L.; Heiman, M.L. Ghrelin induces adiposity in rodents. Nature, 2000, 407, 908-913.
80. St-Pierre, D.H.; Karelis, A.D.; Cianflone, K.; Conus, F.; Mignault, D.; Rabasa-Lhoret, R.; St-Onge, M.; Tremblay-Lebeau, A.; Poehlman, E.T. Relationship between ghrelin and energy expenditure in healthy young women. J. Clin. Endocrinol. Metab., 2004, 89, 5993-5997.
81. Mayorov, A.V.; Amara, N.; Chang, J.Y.; Moss, J.A.; Hixon, M.S.; Ruiz, D.I.; Meijler, M.M.; Zorrilla, E.P.; Janda, K.D. Catalytic antibody degradation of ghrelin increases whole-body metabolic rate and reduces refeeding in fasting mice. PNAS, 2008, 105, 17487-17492.
82. Solomon, A.; De Fanti, B.A.; Martinez, J.A. Peripheral ghrelin interacts with orexin neurons in glucostatic signaling. Regul. Pept., 2007, 144, 17-24.
83. Schneider, S.M.; Al-Jaouni, R.; Caruba, C.; Arab, K.; Suavet, F.; Ferrari, P.; Mothe-Satney, I.; Van Obberghen, E.; Hébuterne, X. Effects of age, malnutrition and refeeding on the expression and secretion of ghrelin. Clin. Nutr., 2008, 27, 724-731.
84. Bauer, J.M.; Haack, A.; Winning, K.; Wirth, R.; Fischer, B.; Uter, W.; Erdmann, J.; Schusdziarra, V.; Sieber, C.C. Impaired postprandial response of active ghrelin and prolonged suppression of hunger sensation in the elderly. J. Gerontol. A Biol. Sci. Med. Sci., 2010, 65, 307-311.
85. Di Francesco, V.; Barazzoni, R.; Bissoli, L.; Fantin, F.; Rizzotti, P.; Residori, L.; Antonioli, A.; Graziani, M.S.; Zanetti, M.; Bosello, O.; Guarnieri, G.; Zamboni, M. The quantity of meal fat influences the profile of postprandial hormones as well as hunger sensation in healthy elderly people. J. Am. Med. Dir. Assoc., 2010, 11, 188-193.
86. Ariyashu, H.; Iwakura, H.; Yamada, G.; Nakao, K.; Kangawa, K.; Akamizu, T. Efficacy of ghrelin as a therapeutic approach for agerelated physiological changes. Endocrinology, 2008, 149, 3722-3728.
87. Reed, J.A.; Benoit, S.C.; Pfluger, P.T.; Tschöp, M.H.; D'Alessio, D.A.; Seeley, R.J. Mice with chronically increased circulating ghrelin develop age-related glucose intolerance. Am. J. Physiol., 2008, 294, E752-E760.
88. Yukawa, M.; Weigle, D.S.; Davis, C.D.; Marck, B.T.; Wolden- Hanson, T. Peripheral ghrelin treatment stabilizes body weight of senescent male Brown Norway rats at baseline and after surgery. Am. J. Physiol., 2008, 294, R1453-R1460.
89. Wu, R.; Zhou, M.; Dong, W.; Ji, Y.; Miksa, M.; Marini, C.P.; Ravikumar, T.S.; Wang, P. Ghrelin hyporesponsiveness contributes o aging-related hyperinflammation in septic shock. Ann. Surg., 2009, 250, 126-133.
90. Székely, M.; Pétervári, E.; Pákai, E.; Hummel, Z.; Szelényi, Z. Acute, subacute and chronic effects of central neuropeptide Y on energy balance in rats. Neuropeptides, 2005, 39, 103-115.
91. Briggs, D.I.; Enriori, P.J.; Lemus, M.B.; Cowley, M.A.; Andrews, Z.B. Diet-induced obesity causes ghrelin resistance in arcuate NPY/AgRP neurons. Endocrinology, 2010, 151, 4745-4755.
92. Li, H.; Matheny, M.; Tümer, N.; Scarpace, P.J. Aging and fasting regulation of leptin and hypothalamic neuropeptide Y gene expression. Am. J. Physiol., 1998, 275, E405-E411.
93. Akimoto-Takano, S.; Sakurai, C.; Kanai, S.; Hosoya, H.; Ohta, M.; Miyasaka, K. Differences in the appetite-stimulating effect of orexin, neuropeptide Y and ghrelin among young, adult and old rats. Neuroendocrinology, 2005, 82, 256-263.
94. Arens, J.; Moar, K.M.; Eiden, S.; Weide, K.; Schmidt, I.; Mercer, J.G.; Simon, E.; Korf, H.-W. Age-dependent hypothalamic expression of neuropeptides in wild-type and melanocortin-4 receptordeficient mice. Physiol. Genomics, 2003, 16, 38-46.
95. Hagan, M.M.; Rushing, P.A.; Pritchard, L.M.; Schwartz, M.W.; Strack, A.M.; Van der Ploeg, L.H.T.; Woods, S.C.; Seeley, R.J. Long-term orexigenic effects of AgRP-(83 132) involve mechanisms other than melanocortin receptor blockade. Am. J. Physiol., 2000, 279, R47-R52.
96. Makimura, H.; Mizuno, T.M.; Mastaitis, J.W.; Agami, R.; Mobbs, C.V. Reducing hypothalamic AGRP by RNA interference increases metabolic rate and decreases body weight without influencing food intake. BMC Neurosci., 2002, 3, 18. doi:10.1186/1471-2202-3-18
97. Redmann, S.M., Jr.; Argyropoulos, G. AgRP deficiency could lead to increased life span. Biochem. Biophys. Res. Commun., 2006, 351, 860-864.
98. Wortley, K.E.; Anderson, K.D.; Yasenchak, J.; Murphy, A.; Valenzuela, D.; Diano, S.; Yancopoulos, G.D.; Wiegand, S.J.; Sleeman, M.W. Agouti-related protein-deficient mice display an age-related lean phenotype. Cell Metab., 2006, 2, 421-427.
99. Székely, M.; Pétervári, E.; Balaskó, M.; Hernádi, I.;Uzsoki, B. Effects of orexins on energy balance and thermoregulation. Regul. Pept., 2002, 104, 47-53.
100. Monda, M.; Viggiano, A.N.; Viggiano, A.; Lanza, A.; De Luca, V. Hyperthermic reactions induced by orexin A: role of the ventromedial hypothalamus. Eur. J. Neurosci., 2005, 22, 1169-1175.
101. Mochizuki, T.; Klerman, E.B.; Sakurai, T.; Scammell, T.E. Elevated body temperature during sleep in orexin knockout mice. Am. J. Physiol., 2006, 291, R533-R540.
102. Székely, M. Orexins, energy balance, temperature, sleep-wake cycle. Am. J. Physiol., 2006, 291, R530-R532.
103. Brownell, S.E.; Conti, B. Age- and gender-specific changes of hypocretin immunopositive neurons in C57BI/6 mice. Neurosci. Lett., 2010, 472, 29-32.
104. Kotz, C.M.; Mullett, M.A.; Wang, C.F. Diminished feeding responsiveness to orexin A (hypocretin 1) in aged rats is accompanied by decreased neuronal activation. Am. J. Physiol., 2005, 289, R359-R366.
105. Tsuneki, H.; Murata, S.; Anzawa, Y.; Soeda, Y.; Tokai, E.; Wada, T.; Kimura, I.; Yanagisawa, M.; Sakurai, T.; Sasaoka, T. Agerelated insulin resistance in hypothalamus and peripheral tissues of orexin knockout mice. Diabetologia, 2008, 51, 657-667.
106. Jeon, J.Y.; Bradley, R.L.; Kokkotou, E.G.; Marino, F.E.; Wang, X.; Pissios, P.; Maratos-Flier, E. MCH-/- mice are resistant to agingassociated increases in body weight and insulin resistance. Diabetes, 2006, 55, 428-434.