Role of Secretin Peptide Family and their Receptors in the Hypothalamic Control of Energy Homeostasis

Abstract

Secretin family of peptide hormones is a group of structurally related brain-gut peptides that exert their functions via interactions with the class B1 G protein-coupled receptors (GPCRs). Recent researches of these peptides and receptors in metabolism have been an area of intense focus for the development of promising drug targets as therapeutic potentials for metabolic disorders. The fact that agonists of GLP-1, a member in the family, have already started being used as therapeutics clearly indicates the importance and relevance of further research on the clinical applications of these peptides. This review aims to provide an overview of the current understanding regarding the importance of this family of peptides as well as their receptors in metabolism with special focus on their actions in the hypothalamus.

Key words

secretin family peptides - energy homeostasis - hypothalamus - secretin family receptors - food intake

• References

• 1 Cardoso JC, Vieira FA, Gomes AS, Power DM. The serendipitous origin of chordate secretin peptide family members. BMC Evol Biol 2010; 10: 135
• 2 Lee VHY, Lee LTO, Chu JYS, Lam IPY, Siu FKY, Vaudry H, Chow BKC. An indispensable role of secretin in mediating the osmoregulatory functions of angiotensin II. FASEB J 2010; 24: 5024-5032
• 3 Borle AB. Regulation of cellular calcium metabolism and calcium transport by calcitonin. J Membr Biol 1975; 21: 125-146
• 4 Laburthe M, Couvineau A, Gaudin P, Maorett JJ, Rouyer-Fessard C, Nicole P. Receptors for VIP, PACAP, Secretin, GRF, Glucagon, GLP-1, and Other Members of Their New Family of G Protein-Linked Receptors: Structure-Function Relationship with Special Reference to the Human VIP-1 Receptora. Ann N Y Acad Sci 1996; 805: 94-109
• 5 Harmar AJ. Family-B G-protein-coupled receptors. Genome Biol 2001; 2: reviews 3013.1-reviews 3013.10
• 6 Archbold JK, Flanagan JU, Watkins HA, Gingell JJ, Hay DL. Structural insights into RAMP modification of secretin family G protein-coupled receptors: implications for drug development. Trends Pharmacol Sci 2011; 32: 591-600
• 7 Watkins HA, Au M, Hay DL. The structure of secretin family GPCR peptide ligands: implications for receptor pharmacology and drug development. Drug Discov Today 2012; 17–18: 1006-1014 Erratum in Drug Discov Today 2013; 18: 312–313
• 8 Poyner DR, Hay DL. Secretin family (Class B) G protein-coupled receptors – from molecular to clinical perspectives. Br J Pharmacol 2012; 166: 1-3
• 9 Furness SG, Wootten D, Christopoulos A, Sexton PM. Consequences of splice variation on Secretin family G protein-coupled receptor function. Br J Pharmacol 2012; 166: 98-109
• 10 de Lecea L, Kilduff T, Peyron C, Gao X-B, Foye P, Danielson P, Fukuhara C, Battenberg E, Gautvik V, Bartlett F. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci USA 1998; 95: 322-327
• 11 Dogrukol-Ak D, Tore F, Tuncel N. Passage of VIP/PACAP/secretin family across the blood-brain barrier: therapeutic effects. Curr Pharm Des 2004; 10: 1325-1340
• 12 Williams G, Bing C, Cai XJ, Harrold JA, King PJ, Liu XH. The hypothalamus and the control of energy homeostasis: different circuits, different purposes. Physiol Behav 2001; 74: 683
• 13 Leibowitz SF, Wortley KE. Hypothalamic control of energy balance: different peptides, different functions. Peptides 2004; 25: 473-504
• 14 Dietrich MO, Horvath TL. Hypothalamic control of energy balance: insights into the role of synaptic plasticity. Trends Neurosci 2013; 36: 65-73
• 15 Morton G, Cummings D, Baskin D, Barsh G, Schwartz M. Central nervous system control of food intake and body weight. Nature 2006; 443: 289-295
• 16 Grill HJ, Kaplan JM. The neuroanatomical axis for control of energy balance. Front Neuroendocrinol 2002; 23: 2-40
• 17 Lopaschuk GD, Ussher JR, Jaswal JS. Targeting Intermediary Metabolism in the Hypothalamus as a Mechanism to Regulate Appetite. Pharmacol Rev 2010; 62: 237-264
• 18 Thorens B. Sensing of glucose in the brain. In: Appetite Control. Joost H-G. (ed.). Springer: Handbook of Experimental Pharmacology; 2012. 209. 277-294
• 19 Burdakov D, Luckman SM, Verkhratsky A. Glucose-sensing neurons of the hypothalamus. Philos Trans R Soc Lond B Biol Sci 2005; 360: 2227-2235
• 20 Parton LE, Ye CP, Coppari R, Enriori PJ, Choi B, Zhang C-Y, Xu C, Vianna CR, Balthasar N, Lee CE. Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity. Nature 2007; 449: 228-232
• 21 Mounien L, Marty N, Tarussio D, Metref S, Genoux D, Preitner F, Foretz M, Thorens B. Glut2-dependent glucose-sensing controls thermoregulation by enhancing the leptin sensitivity of NPY and POMC neurons. FASEB J 2010; 24: 1747-1758
• 22 Lam CK, Chari M, Lam TK. CNS regulation of glucose homeostasis. Physiology 2009; 24: 159-170
• 23 Bayliss WM, Starling EH. The mechanism of pancreatic secretion. J Physiol 1902; 28: 325-353
• 24 Lam IPY, Siu FKY, Chu JYS, Chow BKC. Multiple Actions of Secretin in the Human Body. In: International Review of Cytology. Kwang WJ. (ed.). New York: Academic Press; 2008: 159-190
• 25 Chey WY, Chang T-M. Secretin, 100 years later. J Gastroenterol 2003; 38: 1025-1035
• 26 Ng SS, Yung W, Chow BK. Secretin as a neuropeptide. Mol Neurobiol 2002; 26: 97-107
• 27 Chu JYS, Lee LTO, Lai CH, Vaudry H, Chan YS, Yung WH, Chow BKC. Secretin as a neurohypophysial factor regulating body water homeostasis. Proc Natl Acad Sci USA 2009; 106: 15961-15966
• 28 Chu J, Yung W, Chow B. Secretin: a pleiotrophic hormone. Ann N Y Acad Sci 2006; 1070: 27-50
• 29 O’Donohue TL, Charlton CG, Miller RL, Boden G, Jacobowitz DM. Identification, characterization, and distribution of secretin immunoreactivity in rat and pig brain. Proc Natl Acad Sci USA 1981; 78: 5221-5224
• 30 Samson WK, Lumpkin MD, McCann SM. Presence and possible site of action of secretin in the rat pituitary and hypothalamus. Life Sci 1984; 34: 155-163
• 31 Charlton CG, O’Donohue TL, Miller RL, Jacobowitz DM. Secretin immunoreactivity in rat and pig brain. Peptides 1981; 2 (Suppl. 01) 45-49
• 32 Welch MG, Keune JD, Welch-Horan TB, Anwar N, Anwar M, Ludwig RJ, Ruggiero DA. Secretin: hypothalamic distribution and hypothesized neuroregulatory role in autism. Cell Mol Neurobiol 2004; 24: 219-241
• 33 Tay J, Goulet M, Rusche J, Boismenu R. Age-related and regional differences in secretin and secretin receptor mRNA levels in the rat brain. Neurosci Lett 2004; 366: 176-181
• 34 Cheng CYY, Chu JYS, Chow BKC. Central and Peripheral Administration of Secretin Inhibits Food Intake in Mice through the Activation of the Melanocortin System. Neuropsychopharmacology 2011; 36: 459-471
• 35 Glick Z, Thomas DW, Mayer J. Absence of effect of injections of the intestinal hormones secretin and cholecystokinin-pancreozymin upon feeding behavior. Physiol Behav 1971; 6: 5-8
• 36 Gibbs J, Young RC, Smith GP. Cholecystokinin decreases food intake in rats. J Comp Physiol Psychol 1973; 84: 488-495
• 37 Lorenz DN, Kreielsheimer G, Smith GP. Effect of cholecystokinin, gastrin, secretin and GIP on sham feeding in the rat. Physiol Behav 1979; 23: 1065-1072
• 38 Yang H, Wang L, Wu SV, Tay J, Goulet M, Boismenu R, Czimmer J, Wang Y, Wu S, Ao Y, Taché Y. Peripheral secretin-induced Fos expression in the rat brain is largely vagal dependent. Neuroscience 2004; 128: 131-141
• 39 Chu JY, Cheng CY, Sekar R, Chow BK. Vagal Afferent Mediates the Anorectic Effect of Peripheral Secretin. PloS One 2013; 8: e64859
• 40 Banks WA, Goulet M, Rusche JR, Niehoff ML, Boismenu R. Differential transport of a secretin analog across the blood-brain and blood-cerebrospinal fluid barriers of the mouse. J Pharmacol Exp Therap 2002; 302: 1062-1069
• 41 Li Y, Wu X, Yao H, Owyang C. Secretin activates vagal primary afferent neurons in the rat: evidence from electrophysiological and immunohistochemical studies. Am J Physiol Gastrointest Liver Physiol 2005; 289: G745-G752
• 42 Sekar R, Chow BKC. Metabolic effects of secretin. Gen Comp Endocrinol 2013; 181: 18-24
• 43 Chu JY, Yung WH, Chow BK. Endogenous release of secretin from the hypothalamus. Ann N Y Acad Sci 2006; 1070: 196-200
• 44 Heppner KM, Habegger KM, Day J, Pfluger PT, Perez-Tilve D, Ward B, Gelfanov V, Woods SC, DiMarchi R, Tschöp M. Glucagon regulation of energy metabolism. Physiol Behav 2010; 100: 545-548
• 45 Habegger KM, Heppner KM, Geary N, Bartness TJ, DiMarchi R, Tschop MH. The metabolic actions of glucagon revisited. Nat Rev Endocrinol 2010; 6: 689-697
• 46 Jones BJ, Tan T, Bloom SR. Minireview: Glucagon in Stress and Energy Homeostasis. Endocrinology 2012; 153: 1049-1054
• 47 Penick SB, Hinkle Jr LE. Depression of food intake induced in healthy subjects by glucagon. N Engl J Med 1961; 264: 893-897
• 48 Martin JR, Novin D. Decreased feeding in rats following hepatic-portal infusion of glucagon. Physiol Behav 1977; 19: 461-466
• 49 Geary N, Kissileff HR, Pi-Sunyer FX, Hinton V. Individual, but not simultaneous, glucagon and cholecystokinin infusions inhibit feeding in men. Am J Physiol Regul Integ Comp Physiol 1992; 262: R975-R980
• 50 Geary N, Smith GP. Selective hepatic vagotomy blocks pancreatic glucagon’s satiety effect. Physiol Behav 1983; 31: 391-394
• 51 Morawska D, Sieklucka-Dziuba M, Kleinrok Z. Central action of glucagon. Pol J Pharmacol 1998; 50: 125-133
• 52 Honda K, Kamisoyama H, Uemura T, Yanagi T, Saito N, Kurose Y, Sugahara K, Katoh K, Hasegawa S. The mechanism underlying the central glucagon-induced hyperglycemia and anorexia in chicks. Comp Biochem Physiol A Mol Integ Physiol 2012; 163: 260-264
• 53 Kurose Y, Kamisoyama H, Honda K, Azuma Y, Sugahara K, Hasegawa S, Kobayashi S. Effects of central administration of glucagon on feed intake and endocrine responses in sheep. Anim Sci J 2009; 80: 686-690
• 54 Shimizu H, Egawa M, Yoshimatsu H, Bray GA. Glucagon injected in the lateral hypothalamus stimulates sympathetic activity and suppresses monoamine metabolism. Brain Res 1993; 630: 95-100
• 55 Inokuchi A, Oomura Y, Shimizu N, Yamamoto T. Central action of glucagon in rat hypothalamus. Am J Physiol Regul Integ Comp Physiol 1986; 250: R120-R126
• 56 Hoosein NM, Gurd RS. Identification of glucagon receptors in rat brain. Proc Natl Acad Sci 1984; 81: 4368-4372
• 57 Parker JA, McCullough KA, Field BC, Minnion JS, Martin NM, Ghatei MA, Bloom SR. Glucagon and GLP-1 inhibit food intake and increase c-fos expression in similar appetite regulating centres in the brainstem and amygdala. Int J Obes (Lond) 2013; [Epub ahead of print]
• 58 Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology 2007; 132: 2131-2157
• 59 Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev 2007; 87: 1409-1439
• 60 Kreymann B, Ghatei M, Williams G, Bloom S. Glucagon-like peptide-1 7-36: a physiological incretin in man. Lancet 1987; 330: 1300-1304
• 61 Barrera JG, Sandoval DA, D’Alessio DA, Seeley RJ. GLP-1 and energy balance: an integrated model of short-term and long-term control. Nat Rev Endocrinol 2011; 7: 507-516
• 62 Hayes MR. Neuronal and intracellular signaling pathways mediating GLP-1 energy balance and glycemic effects. Physiol Behav 2012; 106: 413-416
• 63 Hayes MR, De Jonghe BC, Kanoski SE. Role of the glucagon-like-peptide-1 receptor in the control of energy balance. Physiol Behav 2010; 100: 503-510
• 64 Meier JJ, Gallwitz B, Schmidt WE, Nauck MA. Glucagon-like peptide 1 as a regulator of food intake and body weight: therapeutic perspectives. Eur J Pharmacol 2002; 440: 269-279
• 65 Punjabi M, Arnold M, Geary N, Langhans W, Pacheco-López G. Peripheral glucagon-like peptide-1 (GLP-1) and satiation. Physiol Behav 2011; 105: 71-76
• 66 Hayes MR, Kanoski SE, De Jonghe BC, Leichner TM, Alhadeff AL, Fortin SM, Arnold M, Langhans W, Grill HJ. The common hepatic branch of the vagus is not required to mediate the glycemic and food intake suppressive effects of glucagon-like-peptide-1. Am J Physiol Regul Integ Comp Physiol 2011; 301: R1479-R1485
• 67 Nakabayashi H, Nishizawa M, Nakagawa A, Takeda R, Niijima A. Vagal hepatopancreatic reflex effect evoked by intraportal appearance of tGLP-1. Am J Physiol Endocrinol Metabol 1996; 271: E808-E813
• 68 Hayes MR, Bradley L, Grill HJ. Endogenous hindbrain glucagon-like peptide-1 receptor activation contributes to the control of food intake by mediating gastric satiation signaling. Endocrinology 2009; 150: 2654-2659
• 69 Kanoski SE, Fortin SM, Arnold M, Grill HJ, Hayes MR. Peripheral and Central GLP-1 Receptor Populations Mediate the Anorectic Effects of Peripherally Administered GLP-1 Receptor Agonists, Liraglutide and Exendin-4. Endocrinology 2011; 152: 3103-3112
• 70 Turton M, O’shea D, Gunn I, Beak S, Edwards C, Meeran K, Choi S, Taylor G, Heath M, Lambert P. A role for glucagon-like peptide-1 in the central regulation of feeding. Nature 1996; 379: 69-72
• 71 Knauf C, Cani PD, Perrin C, Iglesias MA, Maury JF, Bernard E, Benhamed F, Grémeaux T, Drucker DJ, Kahn CR. Brain glucagon-like peptide-1 increases insulin secretion and muscle insulin resistance to favor hepatic glycogen storage. J Clin Invest 2005; 115: 3554-3563
• 72 Williams DL. Minireview: Finding the Sweet Spot: Peripheral Versus Central Glucagon-Like Peptide 1 Action in Feeding and Glucose Homeostasis. Endocrinology 2009; 150: 2997-3001
• 73 Sandoval DA, Bagnol D, Woods SC, D’Alessio DA, Seeley RJ. Arcuate glucagon-like peptide 1 receptors regulate glucose homeostasis but not food intake. Diabetes 2008; 57: 2046-2054
• 74 Tang-Christensen M, Larsen P, Goke R, Fink-Jensen A, Jessop D, Moller M, Sheikh S. Central administration of GLP-1-(7-36) amide inhibits food and water intake in rats. Am J Physiol Regul Integ Comp Physiol 1996; 271: R848-R856
• 75 Thiele TE, Van Dijk G, Campfield LA, Smith FJ, Burn P, Woods SC, Bernstein IL, Seeley RJ. Central infusion of GLP-1, but not leptin, produces conditioned taste aversions in rats. Am J Physiol Regul Integ Comp Physiol 1997; 272: R726-R730
• 76 McMahon LR, Wellman PJ. PVN infusion of GLP-1-(7–36) amide suppresses feeding but does not induce aversion or alter locomotion in rats. Am J Physiol Regul Integ Comp Physiol 1998; 274: R23-R29
• 77 Kinzig KP, D’Alessio DA, Seeley RJ. The diverse roles of specific GLP-1 receptors in the control of food intake and the response to visceral illness. J Neurosci 2002; 22: 10470-10476
• 78 Kinzig KP, D’Alessio DA, Herman JP, Sakai RR, Vahl TP, Figueiredo HF, Murphy EK, Seeley RJ. CNS glucagon-like peptide-1 receptors mediate endocrine and anxiety responses to interoceptive and psychogenic stressors. J Neurosci 2003; 23: 6163-6170
• 79 Challa TD, Beaton N, Arnold M, Rudofsky G, Langhans W, Wolfrum C. Regulation of adipocyte formation by GLP-1/GLP-1R signaling. J Biol Chem 2012; 287: 6421-6430
• 80 Hayes MR, Skibicka KP, Grill HJ. Caudal Brainstem Processing Is Sufficient for Behavioral, Sympathetic, and Parasympathetic Responses Driven by Peripheral and Hindbrain Glucagon-Like-Peptide-1 Receptor Stimulation. Endocrinology 2008; 149: 4059-4068
• 81 Alhadeff AL, Rupprecht LE, Hayes MR. GLP-1 Neurons in the Nucleus of the Solitary Tract Project Directly to the Ventral Tegmental Area and Nucleus Accumbens to Control for Food Intake. Endocrinology 2012; 153: 647-658
• 82 Dossat AM, Lilly N, Kay K, Williams DL. Glucagon-Like Peptide 1 Receptors in Nucleus Accumbens Affect Food Intake. J Neurosci 2011; 31: 14453-14457
• 83 Goldstone AP, Mercer JG, Gunn I, Moar KM, Edwards CMB, Rossi M, Howard JK, Rasheed S, Turton MD, Small C. Leptin interacts with glucagon-like peptide-1 neurons to reduce food intake and body weight in rodents. FEBS Lett 1997; 415: 134-138
• 84 Scrocchi LA, Drucker DJ. Effects of aging and a high fat diet on body weight and glucose tolerance in glucagon-like peptide-1 receptor−/− mice. Endocrinology 1998; 139: 3127-3132
• 85 Buse JB, Rosenstock J, Sesti G, Schmidt WE, Montanya E, Brett JH, Zychma M, Blonde L. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet 2009; 374: 39-47
• 86 Buse JB, Henry RR, Han J, Kim DD, Fineman MS, Baron AD. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care 2004; 27: 2628-2635
• 87 Kendall DM, Riddle MC, Rosenstock J, Zhuang D, Kim DD, Fineman MS, Baron AD. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care 2005; 28: 1083-1091
• 88 Astrup A, Rössner S, Van Gaal L, Rissanen A, Niskanen L, Al Hakim M, Madsen J, Rasmussen MF, Lean ME. Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study. Lancet 2009; 374: 1606-1616
• 89 Morínigo R, Lacy AM. GLP-1 and changes in glucose tolerance following gastric bypass surgery in morbidly obese subjects. Obes Surg 2006; 16: 1594-1601
• 90 Emeric-Sauval E. Corticotropin-releasing factor (CRF) – a review. Psychoneuroendocrinology 1986; 11: 277-294
• 91 Rivier CL, Plotsky PM. Mediation by corticotropin releasing factor (CRF) of adenohypophysial hormone secretion. Ann Rev Physiol 1986; 48: 475-494
• 92 Liposits Z, Phelix C, Paull W. Synaptic interaction of serotonergic axons and corticotropin releasing factor (CRF) synthesizing neurons in the hypothalamic paraventricular nucleus of the rat. Histochemistry 1987; 86: 541-549
• 93 Dunn AJ, Berridge CW. Physiological and behavioral responses to corticotropin-releasing factor administration: is CRF a mediator of anxiety or stress responses. Brain Res Rev 1990; 15: 100
• 94 Turnbull AV, Rivier C. Corticotropin-releasing factor (CRF) and endocrine responses to stress: CRF receptors, binding protein, and related peptides. In: Proceedings of the Society for Experimental Biology and Medicine Society for Experimental Biology and Medicine. New York, NY: Royal Society of Medicine; 1997: 1-10
• 95 Rothwell NJ. Central effects of CRF on metabolism and energy balance. Neurosci Biobehav Rev 1990; 14: 263-271
• 96 Owens MJ, Nemeroff CB. Physiology and pharmacology of corticotropin-releasing factor. Pharmacol Rev 1991; 43: 425-473
• 97 Tanaka C, Asakawa A, Ushikai M, Sakoguchi T, Amitani H, Terashi M, Cheng K, Chaolu H, Nakamura N, Inui A. Comparison of the anorexigenic activity of CRF family peptides. Biochem Biophy Res Commun 2009; 390: 887-891
• 98 Richard D, Lin Q, Timofeeva E. The corticotropin-releasing factor family of peptides and CRF receptors: their roles in the regulation of energy balance. Eur J Pharmacol 2002; 440: 189-197
• 99 Smith GW, Aubry J-M, Dellu F, Contarino A, Bilezikjian LM, Gold LH, Chen R, Marchuk Y, Hauser C, Bentley CA, Sawchenko PE, Koob GF, Vale W, Lee K-F. Corticotropin Releasing Factor Receptor 1-Deficient Mice Display Decreased Anxiety, Impaired Stress Response, and Aberrant Neuroendocrine Development. Neuron 1998; 20: 1093-1102
• 100 Doyon C, Samson P, Lalonde J, Richard D. Effects of the CRF1 receptor antagonist SSR125543 on energy balance and food deprivation-induced neuronal activation in obese Zucker rats. J Endocrinol 2007; 193: 11-19
• 101 Chao H, Digruccio M, Chen P, Li C. Type 2 Corticotropin-Releasing Factor Receptor in the Ventromedial Nucleus of Hypothalamus Is Critical in Regulating Feeding and Lipid Metabolism in White Adipose Tissue. Endocrinology 2012; 153: 166-176
• 102 Chen P, Van Hover C, Lindberg D, Li C. Central urocortin 3 and type 2 corticotropin-releasing factor receptor in the regulation of energy homeostasis: critical involvement of the ventromedial hypothalamus. Front Endocrinol (Lausanne) 2012; 3: 180, [Epub 2013 Jan 7]
• 103 Carlin KM, Vale WW, Bale TL. Vital functions of corticotropin-releasing factor (CRF) pathways in maintenance and regulation of energy homeostasis. Proc Natl Acad Sci USA 2006; 103: 3462-3467
• 104 Bradbury MJ, McBurnie MI, Denton DA, Lee K-F, Vale WW. Modulation of urocortin-induced hypophagia and weight loss by corticotropin-releasing factor receptor 1 deficiency in mice. Endocrinology 2000; 141: 2715-2724
• 105 Coste SC, Kesterson RA, Heldwein KA, Stevens SL, Heard AD, Hollis JH, Murray SE, Hill JK, Pantely GA, Hohimer AR. Abnormal adaptations to stress and impaired cardiovascular function in mice lacking corticotropin-releasing hormone receptor-2. Nat Gen 2000; 24: 403-409
• 106 Lu X-Y, Barsh GS, Akil H, Watson SJ. Interaction between α-Melanocyte-Stimulating Hormone and Corticotropin-Releasing Hormone in the Regulation of Feeding and Hypothalamo-Pituitary-Adrenal Responses. J Neurosci 2003; 23: 7863-7872
• 107 Kawashima S, Sakihara S, Kageyama K, Nigawara T, Suda T. Corticotropin-releasing factor (CRF) is involved in the acute anorexic effect of a-melanocyte-stimulating hormone: A study using CRF-deficient mice. Peptides 2008; 29: 2169-2174
• 108 Heilig M, Koob GF. A key role for corticotropin-releasing factor in alcohol dependence. Trends Neurosci 2007; 30: 399-406
• 109 Bogdan R, Santesso DL, Fagerness J, Perlis RH, Pizzagalli DA. Corticotropin-releasing hormone receptor type 1 (CRHR1) genetic variation and stress interact to influence reward learning. J Neurosci 2011; 31: 13246-13254
• 110 Cottone P, Sabino V, Roberto M, Bajo M, Pockros L, Frihauf JB, Fekete EM, Steardo L, Rice KC, Grigoriadis DE. CRF system recruitment mediates dark side of compulsive eating. Proc Natl Acad Sci USA 2009; 106: 20016-20020
• 111 Miyata A, Arimura A, Dahl RR, Minamino N, Uehara A, Jiang L, Culler MD, Coy DH. Isolation of a novel 38 residue-hypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells. Biochem Biophys Res Commun 1989; 164: 567-574
• 112 Vaudry D, Gonzalez BJ, Basille M, Yon L, Fournier A, Vaudry H. Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: From Structure to Functions. Pharmacol Rev 2000; 52: 269-324
• 113 Vaudry D, Falluel-Morel A, Bourgault S, Basille M, Burel D, Wurtz O, Fournier A, Chow BKC, Hashimoto H, Galas L, Vaudry H. Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery. Pharmacol Rev 2009; 61: 283-357
• 114 Koves K, Arimura A, Gorcs TG, Somogyvari-Vigh A. Comparative distribution of immunoreactive pituitary adenylate cyclase activating polypeptide and vasoactive intestinal polypeptide in rat forebrain. Neuroendocrinology 1991; 54: 159-169
• 115 Morley JE, Horowitz M, Morley PM, Flood JF. Pituitary adenylate cyclase activating polypeptide (PACAP) reduces food intake in mice. Peptides 1992; 13: 1133-1135
• 116 Dürr K, Norsted E, Gömüç B, Suarez E, Hannibal J, Meister B. Presence of pituitary adenylate cyclase-activating polypeptide (PACAP) defines a subpopulation of hypothalamic POMC neurons. Brain Res 2007; 1186: 203-211
• 117 Mounien L, Bizet P, Boutelet I, Gourcerol G, Fournier A, Vaudry H, Jégou S. Pituitary adenylate cyclase-activating polypeptide directly modulates the activity of proopiomelanocortin neurons in the rat arcuate nucleus. Neuroscience 2006; 143: 155-163
• 118 Mounien L, Bizet P, Boutelet I, Gourcerol G, Basille M, Gonzalez B, Vaudry H, Jegou S. Expression of PACAP Receptor mRNAs by Neuropeptide Y Neurons in the Rat Arcuate Nucleus. Ann N Y Acad Sci 2006; 1070: 457-461
• 119 Nakata M, Kohno D, Shintani N, Nemoto Y, Hashimoto H, Baba A, Yada T. PACAP deficient mice display reduced carbohydrate intake and PACAP activates NPY-containing neurons in the rat hypothalamic arcuate nucleus. Neurosci Lett 2004; 370: 252-256
• 120 Mounien L, Do Rego JC, Bizet P, Boutelet I, Gourcerol G, Fournier A, Brabet P, Costentin J, Vaudry H, Jegou S. Pituitary adenylate cyclase-activating polypeptide inhibits food intake in mice through activation of the hypothalamic melanocortin system. Neuropsychopharmacology 2009; 34: 424-435
• 121 Resch JM, Boisvert JP, Hourigan AE, Mueller CR, Yi SS, Choi S. Stimulation of the hypothalamic ventromedial nuclei by pituitary adenylate cyclase-activating polypeptide induces hypophagia and thermogenesis. Am J Physiol Regul Integ Comp Physiol 2011; 301: R1625-R1634
• 122 Hawke Z, Ivanov TR, Bechtold DA, Dhillon H, Lowell BB, Luckman SM. PACAP Neurons in the Hypothalamic Ventromedial Nucleus Are Targets of Central Leptin Signaling. J Neurosci 2009; 29: 14828-14835
• 123 Adams BA, Gray SL, Isaac ER, Bianco AC, Vidal-Puig AJ, Sherwood NM. Feeding and Metabolism in Mice Lacking Pituitary Adenylate Cyclase-Activating Polypeptide. Endocrinology 2008; 149: 1571-1580
• 124 Sherwood NM, Adams BA, Isaac ER, Wu S, Fradinger EA. Knocked down and out: PACAP in development, reproduction and feeding. Peptides 2007; 28: 1680-1687
• 125 Yi C-X, Sun N, Ackermans MT, Alkemade A, Foppen E, Shi J, Serlie MJ, Buijs RM, Fliers E, Kalsbeek A. Pituitary Adenylate Cyclase-Activating Polypeptide Stimulates Glucose Production via the Hepatic Sympathetic Innervation in Rats. Diabetes 2010; 59: 1591-1600
• 126 Said SI, Mutt V. Isolation from Porcine-Intestinal Wall of a Vasoactive Octacosapeptide Related to Secretin and to Glucagon. Eur J Biochem 1972; 28: 199-204
• 127 Fuxe K, Hökfelt T, Said SI, Mutt V. Vasoactive intestinal polypeptide and the nervous system: Immunohistochemical evidence for localization in central and peripheral neurons, particularly intracortical neurons of the cerebral cortex. Neurosci Lett 1977; 5: 241-246
• 128 Dussaillant M, Sarrieau A, Gozes I, Berod A, Rostene W. Distribution of cells expressing vasoactive intestinal peptide/peptide histidine isoleucine-amide precursor messenger rna in the rat brain. Neuroscience 1992; 50: 519-530
• 129 Usdin TB, Bonner TI, Mezey E. Two receptors for vasoactive intestinal polypeptide with similar specificity and complementary distributions. Endocrinology 1994; 135: 2662-2680
• 130 Alexander LD, Sander LD. Vasoactive intestinal peptide stimulates ACTH and corticosterone release after injection into the PVN. Regul Pept 1994; 51: 221-227
• 131 Alexander LD, Sander LD. Involvement of vasopressin and corticotropin-releasing hormone in VIP- and PHI-induced secretion of ACTH and corticosterone. Neuropeptides 1995; 28: 167-173
• 132 Tachibana T, Saito S, Tomonaga S, Takagi T, Saito E-S, Boswell T, Furuse M. Intracerebroventricular injection of vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide inhibits feeding in chicks. Neurosci Lett 2003; 339: 203-206
• 133 Matsuda K, Maruyama K, Nakamachi T, Miura T, Uchiyama M, Shioda S. Inhibitory effects of pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) on food intake in the goldfish, Carassius auratus. Peptides 2005; 26: 1611-1616
• 134 Ghourab S, Beale KE, Semjonous NM, Simpson KA, Martin NM, Ghatei MA, Bloom SR, Smith KL. Intracerebroventricular administration of vasoactive intestinal peptide inhibits food intake. Regul Pept 2011; 172: 8-15
• 135 Jozsa R, Nemeth J, Tamas A, Hollosy T, Lubics A, Jakab B, Olah A, Lengvari I, Arimura A, Reglödi D. Short-Term Fasting Differentially Alters PACAP and VIP Levels in the Brains of Rat and Chicken. Ann N Y Acad Sci 2006; 1070: 354-358
• 136 Bechtold DA, Brown TM, Luckman SM, Piggins HD. Metabolic rhythm abnormalities in mice lacking VIP-VPAC2 signaling. Am J Physiol Regul Integ Comp Physiol 2008; 294: R344-R351
• 137 Alexander LD, Evans K, Sander LD. A possible involvement of VIP in feeding-induced secretion of ACTH and corticosterone in the Rat. Physiol Behav 1995; 58: 409-413
• 138 Brazeau P, Böhlen P, Esch F, Ling N, Wehrenberg WB, Guillemin R. Growth hormone-releasing factor from ovine and caprine hypothalamus: Isolation, sequence analysis and total synthesis. Biochem Biophys Res Commun 1984; 125: 606-614
• 139 Krulich L, Dhariwal APS, Mccann SM. Stimulatory and Inhibitory Effects of Purified Hypothalamic Extracts on Growth Hormone Release from Rat Pituitary in Vitro. Endocrinology 1968; 83: 783-790
• 140 Esch F, Böhlen P, Ling N, Brazeau P, Guillemin R. Isolation and characterization of the bovine hypothalamic growth hormone releasing factor. Biochem Biophys Res Commun 1983; 117: 772-779
• 141 VandePol CJ, Leidy Jr JW, Finger TE, Robbins RJ. Immunohistochemical localization of GRF-containing neurons in rat brain. Neuroendocrinology 1986; 42: 143-147
• 142 Vaccarino FJ, Feifel D, Rivier J, Vale W, Koob GF. Centrally administered hypothalamic growth hormone-releasing factor stimulates food intake in free-feeding rats. Peptides 1988; 9 (Suppl. 01) 35-38
• 143 Vaccarino FJ, Bloom FE, Rivier J, Vale W, Koob GF. Stimulation of food intake in rats by centrally administered hypothalamic growth hormone-releasing factor. Nature 1985; 314: 167-168
• 144 Sawchenko PE, Swanson LW, Rivier J, Vale WW. The distribution of growth-hormone-releasing factor (GRF) immunoreactivity in the central nervous system of the rat: an immunohistochemical study using antisera directed against rat hypothalamic GRF. J Comp Neurol 1985; 237: 100-115
• 145 Vaccarino FJ, Hayward M. Microinjections of growth hormone-releasing factor into the medial preoptic area/suprachiasmatic nucleus region of the hypothalamus stimulate food intake in rats. Regul Pept 1988; 21: 21-28
• 146 Dickson PR, Vaccarino FJ. Characterization of feeding behavior induced by central injection of GRF. Am J Physiol Regul Integ Comp Physiol 1990; 259: R651-R657
• 147 Dickson PR, Vaccarino FJ. GRF-induced feeding: Evidence for protein selectivity and opiate involvement. Peptides 1994; 15: 1343-1352
• 148 Vaccarino FJ, Buckenham KE. Naloxone blockade of growth hormone-releasing factor-induced feeding. Regul Pept 1987; 18: 165-171
• 149 Vaccarino FJ, Taube MR. Intra-Arcuate Opiate Actions Stimulate GRF-Dependent and Protein-Selective Feeding. Peptides 1997; 18: 197-205
• 150 Rusak B, Zucker I. Neural regulation of circadian rhythms. Physiol Rev 1979; 59: 449-526
• 151 Feifel D, Vaccarino FJ. Feeding effects of growth hormone-releasing factor in rats are photoperiod sensitive. Behav Neurosci 1989; 103: 824-830
• 152 Vaccarino F, Feifel D, Rivier J, Vale W. Antagonism of central growth hormone-releasing factor activity selectively attenuates dark-onset feeding in rats. J Neurosci 1991; 11: 3924-3927
• 153 Dickson PR, Feifel D, Vaccarino FJ. Blockade of endogenous GRF at dark onset selectively suppresses protein intake. Peptides 1995; 16: 7-9
• 154 Feifel D, Vaccarino FJ. Growth hormone-regulatory peptides (GHRH and somatostatin) and feeding: A model for the integration of central and peripheral function. Neurosci Biobehav Rev 1994; 18: 421-433
• 155 Roh J, Chang CL, Bhalla A, Klein C, Hsu SYT. Intermedin Is a Calcitonin/Calcitonin Gene-related Peptide Family Peptide Acting through the Calcitonin Receptor-like Receptor/Receptor Activity-modifying Protein Receptor Complexes. J Biol Chem 2004; 279: 7264-7274
• 156 Poyner DR, Sexton PM, Marshall I, Smith DM, Quirion R, Born W, Muff R, Fischer JA, Foord SM. International Union of Pharmacology. XXXII. The Mammalian Calcitonin Gene-Related Peptides, Adrenomedullin, Amylin, and Calcitonin Receptors. Pharmacol Rev 2002; 54: 233-246
• 157 Lutz TA, Rossi R, Althaus J, Del Prete E, Scharrer E. Amylin reduces food intake more potently than calcitonin gene-related peptide (CGRP) when injected into the lateral brain ventricle in rats. Peptides 1998; 19: 1533-1540
• 158 Flynn JJ, Margules DL, Cooper CW. Presence of immunoreactive calcitonin in the hypothalamus and pituitary lobes of rats. Brain Res Bull 1981; 6: 547-549
• 159 Yamamoto Y, Nakamuta H, Koida M, Seyler JK, Orlowski RC. Calcitonin-induced anorexia in rats: a structure-activity study by intraventricular injections. Jap J Pharmacol 1982; 32: 1013
• 160 Perlow MJ, Freed WJ, Carman JS, Wyatt RJ. Calcitonin reduces feeding in man, monkey and rat. Pharmacol Biochem Behav 1980; 12: 609-612
• 161 Gaggi R, Beltrandi E, Dall’Olio R, Ferri S. Relationships between hypocalcaemic and anorectic effect of calcitonin in the rat. Pharmacol Res Commun 1985; 17: 209-215
• 162 de Beaurepaire R, Freed WJ. Anatomical mapping of the rat hypothalamus for calcitonin-induced anorexia. Pharmacol Biochem Behav 1987; 27: 177-182
• 163 Chelikani PK, Haver AC, Reidelberger RD. Effects of intermittent intraperitoneal infusion of salmon calcitonin on food intake and adiposity in obese rats. Am J Physiol Regul Integ Comp Physiol 2007; 293: R1798-R1808
• 164 Morley JE, Levine AS, Brown DM, Handwerger BS. The effect of calcitonin on food intake in diabetic mice. Peptides 1982; 3: 17-20
• 165 Eiden S, Daniel C, Steinbrueck A, Schmidt I, Simon E. Salmon calcitonin – a potent inhibitor of food intake in states of impaired leptin signalling in laboratory rodents. J Physiol 2002; 541: 1041-1048
• 166 Bello NT, Kemm MH, Moran TH. Salmon calcitonin reduces food intake through changes in meal sizes in male rhesus monkeys. Am J Physiol Regul Integ Comp Physiol 2008; 295: R76-R81
• 167 Zhang Z, Liu X, Morgan DA, Kuburas A, Thedens DR, Russo AF, Rahmouni K. Neuronal Receptor Activity-Modifying Protein 1 Promotes Energy Expenditure in Mice. Diabetes 2011; 60: 1063-1071
• 168 Dhillo WS, Small CJ, Jethwa PH, Russell SH, Gardiner JV, Bewick GA, Seth A, Murphy KG, Ghatei MA, Bloom SR. Paraventricular Nucleus Administration of Calcitonin Gene-Related Peptide Inhibits Food Intake and Stimulates the Hypothalamo-Pituitary-Adrenal Axis. Endocrinology 2003; 144: 1420-1425
• 169 Sun JY, Jing MY, Wang JF, Weng XY. Original Article: The approach to the mechanism of calcitonin gene-related peptide-inducing inhibition of food intake. J Anim Physiol Anim Nutr 2010; 94: 552-560
• 170 Taylor GM, Meeran K, O’Shea D, Smith DM, Ghatei MA, Bloom SR. Adrenomedullin inhibits feeding in the rat by a mechanism involving calcitonin gene-related peptide receptors. Endocrinology 1996; 137: 3260-3264
• 171 Taylor MM, Bagley SL, Samson WK. Intermedin/adrenomedullin-2 acts within central nervous system to elevate blood pressure and inhibit food and water intake. Am J Physiol Regul Integ Comp Physiol 2005; 288: R919-R927
• 172 Sawada H, Yamaguchi H, Shimbara T, Toshinai K, Mondal MS, Date Y, Murakami N, Katafuchi T, Minamino N, Nunoi H, Nakazato M. Central Effects of Calcitonin Receptor-Stimulating Peptide-1 on Energy Homeostasis in Rats. Endocrinology 2006; 147: 2043-2050
• 173 Lutz TA. Amylinergic control of food intake. Physiol Behav 2006; 89: 465-471
• 174 Rushing PA. Central amylin signaling and the regulation of energy homeostasis. Curr Pharmaceut Des 2003; 9: 819-825
• 175 Lutz TA. The role of amylin in the control of energy homeostasis. Am J Physiol Regul Integ Comp Physiol 2010; 298: R1475-R1484
• 176 Lutz T. Control of energy homeostasis by amylin. Cell Mol Life Sci 2012; 69: 1947-1965
• 177 Woods SC, Lutz TA, Geary N, Langhans W. Pancreatic signals controlling food intake; insulin, glucagon and amylin. Philos Trans R Soc Lond B Biol Sci 2006; 361: 1219-1235
• 178 Roth JD, Roland BL, Cole RL, Trevaskis JL, Weyer C, Koda JE, Anderson CM, Parkes DG, Baron AD. Leptin responsiveness restored by amylin agonism in diet-induced obesity: Evidence from nonclinical and clinical studies. Proc Natl Acad Sci USA 2008; 105: 7257-7262
• 179 Turek VF, Trevaskis JL, Levin BE, Dunn-Meynell AA, Irani B, Gu G, Wittmer C, Griffin PS, Vu C, Parkes DG. Mechanisms of amylin/leptin synergy in rodent models. Endocrinology 2010; 151: 143-152
• 180 Mack C, Soares C, Wilson J, Athanacio J, Turek V, Trevaskis J, Roth J, Smith P, Gedulin B, Jodka C. Davalintide (AC2307), a novel amylin-mimetic peptide: enhanced pharmacological properties over native amylin to reduce food intake and body weight. Inter J Obes 2009; 34: 385-395
• 181 Guan X, Shi X, Li X, Chang B, Wang Y, Li D-P, Chan L. GLP-2 receptor in POMC neurons suppresses feeding behavior and gastric motility. Am J Physiol Endocrinol Metab 2012; 303: E853-E864
• 182 Tang-Christensen M, Larsen PJ, Thulesen J, Rømer J, Vrang N. The proglucagon-derived peptide, glucagon-like peptide-2, is a neurotransmitter involved in the regulation of food intake. Nat Med 2000; 6: 802-807
• 183 Dalvi PS, Belsham DD. Glucagon-Like Peptide-2 Directly Regulates Hypothalamic Neurons Expressing Neuropeptides Linked to Appetite Control in Vivo and in Vitro. Endocrinology 2012; 153: 2385-2397
• 184 Lovshin J, Estall J, Yusta B, Brown TJ, Drucker DJ. Glucagon-like peptide (GLP)-2 action in the murine central nervous system is enhanced by elimination of GLP-1 receptor signaling. J Biol Chem 2001; 276: 21489-21499
• 185 Miyawaki K, Yamada Y, Ban N, Ihara Y, Tsukiyama K, Zhou H, Fujimoto S, Oku A, Tsuda K, Toyokuni S. Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Nat Med 2002; 8: 738-742
• 186 Woods S, West D, Stein LJ, McKay L, Lotter EC, Porte SG, Kenney NJ, Porte Jr D. Peptides and the control of meal size. Diabetologia 1981; 20: 305-313
• 187 Gault V, McClean P, Cassidy R, Irwin N, Flatt P. Chemical gastric inhibitory polypeptide receptor antagonism protects against obesity, insulin resistance, glucose intolerance and associated disturbances in mice fed high-fat and cafeteria diets. Diabetologia 2007; 50: 1752-1762
• 188 Ambati S, Duan J, Hartzell DL, Choi Y-H, Della-Fera MA, Baile CA. GIP-dependent expression of hypothalamic genes. Physiol Res/Acad Sci Bohem 2011; 60: 941-950
• 189 Epstein FH, Strewler GJ. The physiology of parathyroid hormone–related protein. N Engl J Med 2000; 342: 177-185
• 190 Asakawa A, Fujimiya M, Niijima A, Fujino K, Kodama N, Sato Y, Kato I, Nanba H, Laviano A, Meguid MM. Parathyroid hormone-related protein has an anorexigenic activity via activation of hypothalamic urocortins 2 and 3. Psychoneuroendocrinology 2010; 35: 1178-1186
• 191 Burtis WJ, Brady TG, Orloff JJ, Ersbak JB, Warrell Jr RP, Olson BR, Wu TL, Mitnick ME, Broadus AE, Stewart AF. Immunochemical characterization of circulating parathyroid hormone-related protein in patients with humoral hypercalcemia of cancer. N Engl J Med 1990; 322: 1106-1112
• 192 McCarty M, Thomas C. PTH excess may promote weight gain by impeding catecholamine-induced lipolysis – implications for the impact of calcium, vitamin D, and alcohol on body weight. Med Hypoth 2003; 61: 535-542