Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Gut hormones such as amylin and GLP-1 in the control of eating and energy expenditure

International Journal of Obesity Supplements volume 6, pages S15–S21 (2016)Cite this article

Subjects

Abstract

The control of meal size is the best studied aspect of the control of energy balance, and manipulation of this system constitutes a promising target to treat obesity. A major part of this control system is based on gastrointestinal hormones such as glucagon-like peptide-1 (GLP-1) or amylin, which are released in response to a meal and which limit the size of an ongoing meal. Both amylin and GLP-1 have also been shown to increase energy expenditure in experimental rodents, but mechanistically we know much less how this effect may be mediated, which brain sites may be involved, and what the physiological relevance of these findings may be. Most studies indicate that the effect of peripheral amylin is centrally mediated via the area postrema, but other brain areas, such as the ventral tegmental area, may also be involved. GLP-1’s effect on eating seems to be mainly mediated by vagal afferents projecting to the caudal hindbrain. Chronic exposure to amylin, GLP-1 or their analogs decrease food intake and body weight gain. Next to the induction of satiation, amylin may also constitute an adiposity signal and in fact interact with the adiposity signal leptin. Amylin analogs are under clinical consideration for their effect to reduce food intake and body weight in humans, and similar to rodents, amylin analogs seem to be particularly active when combined with leptin analogs.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Young A, Denaro M . Roles of amylin in diabetes and in regulation of nutrient load. Nutrition 1998; 14: 524–527.

    Article  CAS  PubMed  Google Scholar 

  2. Lutz TA, Geary N, Szabady MM, Del Prete E, Scharrer E . Amylin decreases meal size in rats. Physiol Behav 1995; 58: 1197–1202.

    Article  CAS  PubMed  Google Scholar 

  3. Boyle CN, Lutz TA . Amylinergic control of food intake in lean and obese rodents. Physiol Behav 2011; 105: 129–137.

    Article  CAS  PubMed  Google Scholar 

  4. Hansen FC, Bueter M, Theis N, Lutz TA, Paulsen S, Dalboge L et al. Hypertrophy dependent doubling of L-cells in Roux-en-Y gastric bypass operated rats. Plos One 2013; 8: e65696.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ezcurra M, Reimann F, Gribble FM, Emery E . Molecular mechanisms of incretin hormone secretion. Curr Opin Pharmacol 2013; 13: 922–927.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Chambers AP, Jessen L, Ryan KK, Sisley S, Wilson-Perez HE, Stefater MA et al. Weight-independent changes in blood glucose homeostasis after gastric bypass or vertical sleeve gastrectomy in rats. Gastroenterology 2011; 141: 950–958.

    Article  CAS  PubMed  Google Scholar 

  7. Jorgensen NB, Dirksen C, Bojsen-Moller KN, Jacobsen SH, Worm D, Hansen DL et al. Exaggerated glucagon-like peptide 1 response is important for improved beta-cell function and glucose tolerance after Roux-en-Y gastric bypass in patients with type 2 diabetes. Diabetes 2013; 62: 3044–3052.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. le Roux CW, Aylwin SJ, Batterham RL, Borg CM, Coyle F, Prasad V et al. Gut hormone profiles following bariatric surgery favor an anorectic state, facilitate weight loss, and improve metabolic parameters. Ann Surg 2006; 243: 108–114.

    Article  PubMed  Google Scholar 

  9. Mumphrey MB, Patterson LM, Zheng H, Berthoud HR . Roux-en-Y gastric bypass surgery increases number but not density of CCK-, GLP-1-, 5-HT-, and neurotensin-expressing enteroendocrine cells in rats. Neurogastroenterol Motil 2013; 25: e70–e79.

    Article  CAS  PubMed  Google Scholar 

  10. Bueter M, Lowenstein C, Olbers T, Wang M, Cluny NL, Bloom SR et al. Gastric bypass increases energy expenditure in rats. Gastroenterology 2010; 138: 1845–1853.

    Article  PubMed  Google Scholar 

  11. Osto E, Doytcheva P, Corteville C, Bueter M, Dorig C, Stivala S et al. Rapid and body weight-independent improvement of endothelial and HDL function after Roux-en-Y gastric bypass: role of glucagon-like peptide-1. Circulation 2015; (131: 871–878.

    Article  CAS  PubMed  Google Scholar 

  12. Rinaman L . A functional role for central glucagon-like peptide-1 receptors in lithium chloride-induced anorexia. Am J Physiol 1999; 277 (5 Pt 2): R1537–R1540.

    CAS  PubMed  Google Scholar 

  13. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hisadome K, Reimann F, Gribble FM, Trapp S. CCK . stimulation of GLP-1 neurons involves alpha1-adrenoceptor-mediated increase in glutamatergic synaptic inputs. Diabetes 2011; 60: 2701–2709.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Richards P, Parker HE, Adriaenssens AE, Hodgson JM, Cork SC, Trapp S et al. Identification and characterization of GLP-1 receptor-expressing cells using a new transgenic mouse model. Diabetes 2014; 63: 1224–1233.

    Article  CAS  PubMed  Google Scholar 

  16. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Lutz TA . The role of amylin in the control of energy homeostasis. Am J Physiol Regul Integr Comp Physiol 2010; 298: R1475–R1484.

    Article  CAS  PubMed  Google Scholar 

  18. Geary N . A new way of looking at eating. Am J Physiol Regul Integr Comp Physiol 2005; 288: R1444–R1446.

    Article  CAS  PubMed  Google Scholar 

  19. Lutz TA, Geary N Gastrointestinal factors in Appetite and Food Research—Animal Research. In: Harris R, Mattes R (eds). Appetite and Food Intake: Behavioral and Physiological Consideration. CRC Press, Taylor & Francis Group: Boca Raton, London, New York, 2008, pp 163–186.

  20. Reidelberger RD, Arnelo U, Granqvist L, Permert J . Comparative effects of amylin and cholecystokinin on food intake and gastric emptying in rats. Am J Physiol Regul Integr Comp Physiol 2001; 280: R605–R611.

    Article  CAS  PubMed  Google Scholar 

  21. Reidelberger RD, Kelsey L, Heimann D . Effects of amylin-related peptides on food intake, meal patterns, and gastric emptying in rats. Am J Physiol Regul Integr Comp Physiol 2002; 282: R1395–R1404.

    Article  CAS  PubMed  Google Scholar 

  22. Rushing PA, Seeley RJ, Air EL, Lutz TA, Woods SC . Acute 3rd-ventricular amylin infusion potently reduces food intake but does not produce aversive consequences. Peptides 2002; 23: 985–988.

    Article  CAS  PubMed  Google Scholar 

  23. Ruttimann EB, Arnold M, Hillebrand JJ, Geary N, Langhans W . Intrameal hepatic portal and intraperitoneal infusions of glucagon-like peptide-1 reduce spontaneous meal size in the rat via different mechanisms. Endocrinology 2009; 150: 1174–1181.

    Article  CAS  PubMed  Google Scholar 

  24. Chelikani PK, Haver AC, Reidelberger RD . Intravenous infusion of glucagon-like peptide-1 potently inhibits food intake, sham feeding, and gastric emptying in rats. Am J Physiol Regul Integr Comp Physiol 2005; 288: R1695–R1706.

    Article  CAS  PubMed  Google Scholar 

  25. Mollet A, Gilg S, Riediger T, Lutz TA . Infusion of the amylin antagonist AC 187 into the area postrema increases food intake in rats. Physiol Behav 2004; 81: 149–155.

    Article  CAS  PubMed  Google Scholar 

  26. Williams DL, Baskin DG, Schwartz MW . Evidence that intestinal glucagon-like peptide-1 plays a physiological role in satiety. Endocrinology 2009; 150: 1680–1687.

    Article  CAS  PubMed  Google Scholar 

  27. Ruttimann EB, Arnold M, Geary N, Langhans W . GLP-1 antagonism with exendin (9-39) fails to increase spontaneous meal size in rats. Physiol Behav 2010; 100: 291–296.

    Article  CAS  PubMed  Google Scholar 

  28. Steinert RE, Schirra J, Meyer-Gerspach AC, Kienle P, Fischer H, Schulte F et al. Effect of glucagon-like peptide-1 receptor antagonism on appetite and food intake in healthy men. Am J Clin Nutr 2014; 100: 514–523.

    Article  CAS  PubMed  Google Scholar 

  29. Melhorn SJ, Tyagi V, Smeraglio A, Roth CL, Schur EA . Initial evidence that GLP-1 receptor blockade fails to suppress postprandial satiety or promote food intake in humans. Appetite 2014; 82: 85–90.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Lutz TA, Mollet A, Rushing PA, Riediger T, Scharrer E . The anorectic effect of a chronic peripheral infusion of amylin is abolished in area postrema/nucleus of the solitary tract (AP/NTS) lesioned rats. Int J Obes Relat Metab Disord 2001; 25: 1005–1011.

    Article  CAS  PubMed  Google Scholar 

  31. Arnelo U, Permert J, Adrian TE, Larsson J, Westermark P, Reidelberger RD . Chronic infusion of islet amyloid polypeptide causes anorexia in rats. Am J Physiol 1996; 271 (6 Pt 2): R1654–R1659.

    CAS  PubMed  Google Scholar 

  32. Mells JE, Fu PP, Sharma S, Olson D, Cheng L, Handy JA et al. Glp-1 analog, liraglutide, ameliorates hepatic steatosis and cardiac hypertrophy in C57BL/6J mice fed a Western diet. Am J Physiol Gastrointest Liver Physiol 2012; 302: G225–G235.

    Article  CAS  PubMed  Google Scholar 

  33. Rowland NE, Crews EC, Gentry RM . Comparison of Fos induced in rat brain by GLP-1 and amylin. Regul Pept 1997; 71: 171–174.

    Article  CAS  PubMed  Google Scholar 

  34. Zuger D, Forster K, Lutz TA, Riediger T . Amylin and GLP-1 target different populations of area postrema neurons that are both modulated by nutrient stimuli. Physiol Behav 2013; 112–113: 61–69.

    Article  PubMed  CAS  Google Scholar 

  35. Baumgartner I, Pacheco-Lopez G, Ruttimann EB, Arnold M, Asarian L, Langhans W et al. Hepatic-portal vein infusions of glucagon-like peptide-1 reduce meal size and increase c-Fos expression in the nucleus tractus solitarii, area postrema and central nucleus of the amygdala in rats. J Neuroendocrinol 2010; 22: 557–563.

    Article  CAS  PubMed  Google Scholar 

  36. Riediger T, Zuend D, Becskei C, Lutz TA . The anorectic hormone amylin contributes to feeding-related changes of neuronal activity in key structures of the gut-brain axis. Am J Physiol Regul Integr Comp Physiol 2004; 286: R114–R122.

    Article  CAS  PubMed  Google Scholar 

  37. Mack CM, Soares CJ, Wilson JK, Athanacio JR, Turek VF, Trevaskis JL et al. Davalintide (AC2307), a novel amylin-mimetic peptide: enhanced pharmacological properties over native amylin to reduce food intake and body weight. Int J Obes 2010; 34: 385–395.

    Article  CAS  Google Scholar 

  38. Lutz TA, Senn M, Althaus J, Del Prete E, Ehrensperger F, Scharrer E . Lesion of the area postrema/nucleus of the solitary tract (AP/NTS) attenuates the anorectic effects of amylin and calcitonin gene-related peptide (CGRP) in rats. Peptides 1998; 19: 309–317.

    Article  CAS  PubMed  Google Scholar 

  39. Potes CS, Turek VF, Cole RL, Vu C, Roland BL, Roth JD et al. Noradrenergic neurons of the area postrema mediate amylin’s hypophagic action. Am J Physiol Regul Integr Comp Physiol 2010; 299: R623–R631.

    Article  CAS  PubMed  Google Scholar 

  40. Edwards GL, Gedulin BR, CJ, Dilts RP, CCM, Young A . Area postrem (AP)-lesions block the regulation of gastric emptying by amylin. Neurogastroenterol Motil 1998; 10.

  41. Wickbom J, Herrington MK, Permert J, Jansson A, Arnelo U . Gastric emptying in response to IAPP and CCK in rats with subdiaphragmatic afferent vagotomy. Regul Pept 2008; 148: 21–25.

    Article  CAS  PubMed  Google Scholar 

  42. Lutz TA, Althaus J, Rossi R, Scharrer E . Anorectic effect of amylin is not transmitted by capsaicin-sensitive nerve fibers. Am J Physiol 1998; 274 (6 Pt 2): R1777–R1782.

    CAS  PubMed  Google Scholar 

  43. Lutz TA, Del Prete E, Scharrer E . Reduction of food intake in rats by intraperitoneal injection of low doses of amylin. Physiol Behav 1994; 55: 891–895.

    Article  CAS  PubMed  Google Scholar 

  44. Lutz TA, Del Prete E, Scharrer E . Subdiaphragmatic vagotomy does not influence the anorectic effect of amylin. Peptides 1995; 16: 457–462.

    Article  CAS  PubMed  Google Scholar 

  45. Mietlicki-Baase EG, Hayes MR . Amylin activates distributed CNS nuclei to control energy balance. Physiol Behav 2014; 136: 39–46.

    Article  CAS  PubMed  Google Scholar 

  46. Lutz TA, Tschudy S, Rushing PA, Scharrer E . Amylin receptors mediate the anorectic action of salmon calcitonin (sCT). Peptides 2000; 21: 233–238.

    Article  CAS  PubMed  Google Scholar 

  47. Mietlicki-Baase EG, Rupprecht LE, Olivos DR, Zimmer DJ, Alter MD, Pierce RC et al. Amylin receptor signaling in the ventral tegmental area is physiologically relevant for the control of food intake. Neuropsychopharmacology 2013; 38: 1685–1697.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Banks WA, Kastin AJ . Differential permeability of the blood-brain barrier to two pancreatic peptides: insulin and amylin. Peptides 1998; 19: 883–889.

    Article  CAS  PubMed  Google Scholar 

  49. Banks WA, Kastin AJ, Maness LM, Huang W, Jaspan JB . Permeability of the blood-brain barrier to amylin. Life Sci 1995; 57: 1993–2001.

    Article  CAS  PubMed  Google Scholar 

  50. Bailey R, Walker C, Ferner A, Loomes K, Prijic G, Halim A et al. Pharmacological characterization of rat amylin receptors: implications for the identification of amylin receptor subtypes. Br J Pharmacol 2012; 166: 151–167.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Punjabi M, Arnold M, Ruttimann E, Graber M, Geary N, Pacheco-Lopez G et al. Circulating glucagon-like peptide-1 (GLP-1) inhibits eating in male rats by acting in the hindbrain and without inducing avoidance. Endocrinology 2014; 155: 1690–1699.

    Article  PubMed  CAS  Google Scholar 

  52. Bailey RJ, Walker CS, Ferner AH, Loomes KM, Prijic G, Halim A et al. Pharmacological characterization of rat amylin receptors: implications for the identification of amylin receptor subtypes. Br J Pharmacol 2012; 166: 151–167.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. McLatchie LM, Fraser NJ, Main MJ, Wise A, Brown J, Thompson N et al. RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature 1998; 393: 333–339.

    Article  CAS  PubMed  Google Scholar 

  54. Hay DL, Christopoulos G, Christopoulos A, Poyner DR, Sexton PM . Pharmacological discrimination of calcitonin receptor: receptor activity-modifying protein complexes. Mol Pharmacol 2005; 67: 1655–1665.

    Article  CAS  PubMed  Google Scholar 

  55. Sexton PM, Paxinos G, Kenney MA, Wookey PJ, Beaumont K . In vitro autoradiographic localization of amylin binding sites in rat brain. Neuroscience 1994; 62: 553–567.

    Article  CAS  PubMed  Google Scholar 

  56. Becskei C, Riediger T, Zund D, Wookey P, Lutz TA . Immunohistochemical mapping of calcitonin receptors in the adult rat brain. Brain Res 2004; 1030: 221–233.

    Article  CAS  PubMed  Google Scholar 

  57. Barth SW, Riediger T, Lutz TA, Rechkemmer G . Peripheral amylin activates circumventricular organs expressing calcitonin receptor a/b subtypes and receptor-activity modifying proteins in the rat. Brain Res 2004; 997: 97–102.

    Article  CAS  PubMed  Google Scholar 

  58. Ueda T, Ugawa S, Saishin Y, Shimada S . Expression of receptor-activity modifying protein (RAMP) mRNAs in the mouse brain. Brain Res Mol Brain Res 2001; 93: 36–45.

    Article  CAS  PubMed  Google Scholar 

  59. Liberini CG, Boyle CN, Cifani C, Venniro M, Hope BT, Lutz TA . Amylin receptor components and the leptin receptor are co-expressed in single rat area postrema neurons. Eur J Neurosci 2016; 43: 653–661.

    Article  PubMed  Google Scholar 

  60. Riediger T, Schmid HA, Lutz T, Simon E . Amylin potently activates AP neurons possibly via formation of the excitatory second messenger cGMP. Am J Physiol Regul Integr Comp Physiol 2001; 281: R1833–R1843.

    Article  CAS  PubMed  Google Scholar 

  61. Potes CS, Boyle CN, Wookey PJ, Riediger T, Lutz TA . Involvement of the extracellular signal-regulated kinase 1/2 signaling pathway in amylin’s eating inhibitory effect. Am J Physiol Regul Integr Comp Physiol 2012; 302: R340–R351.

    Article  CAS  PubMed  Google Scholar 

  62. Braegger FE, Asarian L, Dahl K, Lutz TA, Boyle CN . The role of the area postrema in the anorectic effects of amylin and salmon calcitonin: behavioral and neuronal phenotyping. Eur J Neurosci 2014; 40: 3055–3066.

    Article  PubMed  Google Scholar 

  63. Ronveaux CC, de Lartigue G, Raybould HE . Ability of GLP-1 to decrease food intake is dependent on nutritional status. Physiol Behav 2014; 135: 222–229.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Michel S, Becskei C, Erguven E, Lutz TA, Riediger T . Diet-derived nutrients modulate the effects of amylin on c-Fos expression in the area postrema and on food intake. Neuroendocrinology 2007; 86: 124–135.

    Article  CAS  PubMed  Google Scholar 

  65. Wielinga PY, Alder B, Lutz TA . The acute effect of amylin and salmon calcitonin on energy expenditure. Physiol Behav 2007; 91: 212–217.

    Article  CAS  PubMed  Google Scholar 

  66. Wielinga PY, Löwenstein C, Alder B, Lutz TA . Effect of peripheral and central amylin on energy expenditure and body temperature. Appetite 2008; 91: 409.

    Google Scholar 

  67. Fernandes-Santos C, Zhang Z, Morgan DA, Guo DF, Russo AF, Rahmouni K . Amylin acts in the central nervous system to increase sympathetic nerve activity. Endocrinology 2013; 154: 2481–2488.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Osaka T, Tsukamoto A, Koyama Y, Inoue S . Central and peripheral administration of amylin induces energy expenditure in anesthetized rats. Peptides 2008; 29: 1028–1035.

    Article  CAS  PubMed  Google Scholar 

  69. Wielinga PY, Lowenstein C, Muff S, Munz M, Woods SC, Lutz TA . Central amylin acts as an adiposity signal to control body weight and energy expenditure. Physiol Behav 2010; 101: 45–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Abegg K, Schiesser M, Lutz TA, Bueter M . Acute peripheral GLP-1 receptor agonism or antagonism does not alter energy expenditure in rats after Roux-en-Y gastric bypass. Physiol Behav 2013; 121: 70–78.

    Article  CAS  PubMed  Google Scholar 

  71. Osaka T, Endo M, Yamakawa M, Inoue S . Energy expenditure by intravenous administration of glucagon-like peptide-1 mediated by the lower brainstem and sympathoadrenal system. Peptides 2005; 26: 1623–1631.

    Article  CAS  PubMed  Google Scholar 

  72. Heruc GA, Horowitz M, Deacon CF, Feinle-Bisset C, Rayner CK, Luscombe-Marsh N et al. Effects of dipeptidyl peptidase IV inhibition on glycemic, gut hormone, triglyceride, energy expenditure, and energy intake responses to fat in healthy males. Am J Physiol Endocrinol Metab 2014; 307: E830–E837.

    Article  CAS  PubMed  Google Scholar 

  73. Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG . Central nervous system control of food intake. Nature 2000; 404: 661–671.

    Article  CAS  PubMed  Google Scholar 

  74. Asarian L, Geary N . Sex differences in the physiology of eating. Am J Physiol Regul Integr Comp Physiol 2013; 305: R1215–R1267.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. 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 (Pt 3): 1041–1048.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Osto M, Wielinga PY, Alder B, Walser N, Lutz TA . Modulation of the satiating effect of amylin by central ghrelin, leptin and insulin. Physiol Behav 2007; 91: 566–572.

    Article  CAS  PubMed  Google Scholar 

  77. Friedman JM . Leptin, leptin receptors and the control of body weight. Eur J Med Res 1997; 2: 7–13.

    CAS  PubMed  Google Scholar 

  78. Leibel RL . The role of leptin in the control of body weight. Nutr Rev 2002; 60 (10 Pt 2): S15–S19.

    Article  PubMed  Google Scholar 

  79. Myers MG, Cowley MA, Munzberg H . Mechanisms of leptin action and leptin resistance. Annu Rev Physiol 2008; 70: 537–556.

    Article  CAS  PubMed  Google Scholar 

  80. Zhang Y, Scarpace PJ . The role of leptin in leptin resistance and obesity. Physiol Behav 2006; 88: 249–256.

    Article  CAS  PubMed  Google Scholar 

  81. Roth JD, Roland BL, Cole RL, Trevaskis JL, Weyer C, Koda JE et al. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Boyle CN, Rossier MM, Lutz TA . Diet-induced obesity, hyperamylinemia and amylin sensitivity. Appetite 2010; 54: 636.

    Google Scholar 

  83. Boyle CN, Rossier MM, Lutz TA . Influence of high-fat feeding, diet-induced obesity, and hyperamylinemia on the sensitivity to acute amylin. Physiol Behav 2011; 104: 20–28.

    Article  CAS  PubMed  Google Scholar 

  84. Trevaskis J, Coffey T, Cole R, Lei C, Wittmer C, Walsh B et al. Amylin-mediated restoration of leptin responsiveness in diet-induced obesity: magnitude and mechanisms. Endocrinology 2008; 149: 5679–5687.

    Article  CAS  PubMed  Google Scholar 

  85. Turek VF, Trevaskis JL, Levin BE, Dunn-Meynell AA, Irani B, Gu G et al. Mechanisms of amylin/leptin synergy in rodent models. Endocrinology 2010; 151: 143–152.

    Article  CAS  PubMed  Google Scholar 

  86. Seth R, Knight WD, Overton JM . Combined amylin-leptin treatment lowers blood pressure and adiposity in lean and obese rats. Int J Obes 2011; 35: 1183–1192.

    Article  CAS  Google Scholar 

  87. Reidelberger R, Haver A, Chelikani PK, Apenteng B, Perriotte-Olson C, Anders K et al. Effects of leptin replacement alone and with exendin-4 on food intake and weight regain in weight-reduced diet-induced obese rats. Am J Physiol Endocrinol Metab 2012; 302: E1576–E1585.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Zhao S, Kanoski SE, Yan J, Grill HJ, Hayes MR . Hindbrain leptin and glucagon-like-peptide-1 receptor signaling interact to suppress food intake in an additive manner. Int J Obes 2012.

  89. Muller TD, Sullivan LM, Habegger K, Yi CX, Kabra D, Grant E et al. Restoration of leptin responsiveness in diet-induced obese mice using an optimized leptin analog in combination with exendin-4 or FGF21. J Pept Sci 2012; 18: 383–393.

    Article  CAS  PubMed  Google Scholar 

  90. Ashwell M, Meade CJ . Obesity: do fat cells from genetically obese mice (C57BL/6J ob/ob) have an innate capacity for increased fat storage? Diabetologia 1978; 15: 465–470.

    Article  CAS  PubMed  Google Scholar 

  91. Mack C, Wilson J, Athanacio J, Reynolds J, Laugero K, Guss S et al. Pharmacological actions of the peptide hormone amylin in the long-term regulation of food intake, food preference, and body weight. Am J Physiol Regul Integr Comp Physiol 2007; 293: R1855–R1863.

    Article  CAS  PubMed  Google Scholar 

  92. Trevaskis JL, Lei C, Koda JE, Weyer C, Parkes DG, Roth JD . Interaction of leptin and amylin in the long-term maintenance of weight loss in diet-induced obese rats. Obesity (Silver Spring) 2010; 18: 21–26.

    Article  CAS  Google Scholar 

  93. Trevaskis JL, Parkes DG, Roth JD . Insights into amylin-leptin synergy. Trends Endocrinol Metab 2010; 21: 473–479.

    Article  CAS  PubMed  Google Scholar 

  94. Lutz TA . The interaction of amylin with other hormones in the control of eating. Diabetes Obes Metab 2013; 15: 99–111.

    Article  CAS  PubMed  Google Scholar 

  95. Seth R, Terry DE, Parrish B, Bhatt R, Overton JM . Amylin-leptin coadministration stimulates central histaminergic signaling in rats. Brain Res 2012; 1442: 15–24.

    Article  CAS  PubMed  Google Scholar 

  96. Moon HS, Chamberland JP, Diakopoulos KN, Fiorenza CG, Ziemke F, Schneider B et al. Leptin and amylin act in an additive manner to activate overlapping signaling pathways in peripheral tissues; in vitro and ex vivo studies in humans. Diabetes Care 2011; 34: 132–138.

    Article  CAS  PubMed  Google Scholar 

  97. Moon HS, Chamberland JP, Mantzoros CS . Amylin and leptin activate overlapping signalling pathways in an additive manner in mouse GT1-7 hypothalamic, CC muscle and AML12 liver cell lines. Diabetologia 2012; 55: 215–225.

    Article  CAS  PubMed  Google Scholar 

  98. Le Foll C, Johnson MD, Dunn-Meynell A, Boyle CN, Lutz TA, Levin BE . Amylin-induced central IL-6 production enhances ventromedial hypothalamic leptin signaling. Diabetes 2015; 64: 1621–1631.

    Article  CAS  PubMed  Google Scholar 

  99. Bhavsar S, Watkins J, Young A . Synergy between amylin and cholecystokinin for inhibition of food intake in mice. Physiol Behav 1998; 64: 557–561.

    Article  CAS  PubMed  Google Scholar 

  100. Trevaskis JL, Turek VF, Griffin PS, Wittmer C, Parkes DG, Roth JD . Multi-hormonal weight loss combinations in diet-induced obese rats: therapeutic potential of cholecystokinin? Physiol Behav 2010; 100: 187–195.

    Article  CAS  PubMed  Google Scholar 

  101. Lutz TA, Del Prete E, Szabady MM, Scharrer E . Attenuation of the anorectic effects of glucagon, cholecystokinin, and bombesin by the amylin receptor antagonist CGRP(8-37). Peptides 1996; 17: 119–124.

    Article  CAS  PubMed  Google Scholar 

  102. Lutz TA, Tschudy S, Rushing PA, Scharrer E . Attenuation of the anorectic effects of cholecystokinin and bombesin by the specific amylin antagonist AC 253. Physiol Behav 2000; 70: 533–536.

    Article  CAS  PubMed  Google Scholar 

  103. Mollet A, Meier S, Grabler V, Gilg S, Scharrer E, Lutz TA . Endogenous amylin contributes to the anorectic effects of cholecystokinin and bombesin. Peptides 2003; 24: 91–98.

    Article  CAS  PubMed  Google Scholar 

  104. Asarian L, Geary N . Estradiol enhances cholecystokinin-dependent lipid-induced satiation and activates estrogen receptor-alpha-expressing cells in the nucleus tractus solitarius of ovariectomized rats. Endocrinology 2007; 148: 5656–5666.

    Article  CAS  PubMed  Google Scholar 

  105. Asarian L, Geary N . Cyclic estradiol treatment phasically potentiates endogenous cholecystokinin’s satiating action in ovariectomized rats. Peptides 1999; 20: 445–450.

    Article  CAS  PubMed  Google Scholar 

  106. Thammacharoen S, Lutz TA, Geary N, Asarian L . Hindbrain administration of estradiol inhibits feeding and activates estrogen receptor-alpha-expressing cells in the nucleus tractus solitarius of ovariectomized rats. Endocrinology 2008; 149: 1609–1617.

    Article  CAS  PubMed  Google Scholar 

  107. Trevaskis JL, Turek VF, Wittmer C, Griffin PS, Wilson JK, Reynolds JM et al. Enhanced amylin-mediated body weight loss in estradiol-deficient diet-induced obese rats. Endocrinology 2010; 151: 5657–5668.

    Article  CAS  PubMed  Google Scholar 

  108. Asarian L, Boyle CN, Lutz TA . Estradiol (E2) increases the acute eating-inhibitory effect of amylin in ovariectomized (OVX) rats. Appetite 2011; 57S: S2.

    Article  Google Scholar 

  109. Lutz TA . Amylin may offer (more) help to treat postmenopausal obesity. Endocrinology 2011; 152: 1–3.

    Article  CAS  PubMed  Google Scholar 

  110. Schwenk RW, Baumeier C, Finan B, Kluth O, Brauer C, Joost HG et al. GLP-1-oestrogen attenuates hyperphagia and protects from beta cell failure in diabetes-prone New Zealand obese (NZO) mice. Diabetologia 2015; 58: 604–614.

    Article  CAS  PubMed  Google Scholar 

  111. Hollander P, Maggs DG, Ruggles JA, Fineman M, Shen L, Kolterman OG et al. Effect of pramlintide on weight in overweight and obese insulin-treated type 2 diabetes patients. Obes Res 2004; 12: 661–668.

    Article  CAS  PubMed  Google Scholar 

  112. Chapman I, Parker B, Doran S, Feinle-Bisset C, Wishart J, Lush CW et al. Low-dose pramlintide reduced food intake and meal duration in healthy, normal-weight subjects. Obesity (Silver Spring) 2007; 15: 1179–1186.

    Article  CAS  Google Scholar 

  113. Aronne L, Fujioka K, Aroda V, Chen K, Halseth A, Kesty NC et al. Progressive reduction in body weight after treatment with the amylin analog pramlintide in obese subjects: a phase 2, randomized, placebo-controlled, dose-escalation study. J Clin Endocrinol Metab 2007; 92: 2977–2983.

    Article  CAS  PubMed  Google Scholar 

  114. Smith SR, Blundell JE, Burns C, Ellero C, Schroeder BE, Kesty NC et al. Pramlintide treatment reduces 24-h caloric intake and meal sizes and improves control of eating in obese subjects: a 6-wk translational research study. Am J Physiol Endocrinol Metab 2007; 293: E620–E627.

    Article  CAS  PubMed  Google Scholar 

  115. Smith SR, Aronne LJ, Burns CM, Kesty NC, Halseth AE, Weyer C . Sustained weight loss following 12-month pramlintide treatment as an adjunct to lifestyle intervention in obesity. Diabetes Care 2008; 31: 1816–1823.

    Article  PubMed  PubMed Central  Google Scholar 

  116. Ravussin E, Smith SR, Mitchell JA, Shringarpure R, Shan K, Maier H et al. Enhanced weight loss with pramlintide/metreleptin: an integrated neurohormonal approach to obesity pharmacotherapy. Obesity (Silver Spring) 2009; 17: 1736–1743.

    Article  CAS  Google Scholar 

  117. Bello NT, Kemm MH, Ofeldt EM, Moran TH . Dose combinations of exendin-4 and salmon calcitonin produce additive and synergistic reductions in food intake in nonhuman primates. Am J Physiol Regul Integr Comp Physiol 2010; 299: R945–R952.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Rossger K, Charpin-El-Hamri G, Fussenegger M . A closed-loop synthetic gene circuit for the treatment of diet-induced obesity in mice. Nat Commun 2013; 4: 2825.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The continued financial support of our amylin-directed research by the Swiss National Science Foundation, the support by the Zurich Center of Integrative Human Physiology, the Stiftung für wissenschaftliche Forschung der Universität Zürich, the Novartis Foundation, the Ciba-Geigy Foundation, the Olga Mayenfisch Foundation, the EMDO foundation and the Vontobel Foundation are gratefully acknowledged. The publication of this article was sponsored by the Université Laval’s Research Chair in Obesity in an effort to inform the public on the causes, consequences, treatments and prevention of obesity.

Author information

Authors and Affiliations

  1. Institute of Veterinary Physiology, Vetsuisse Faculty University of Zurich, Zurich, Switzerland

    T A Lutz

  2. Zurich Center of Integrative Human Physiology, University of Zurich, Zurich, Switzerland

    T A Lutz

Authors
  1. T A Lutz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T A Lutz.

Ethics declarations

Competing interests

The author declared no competing interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lutz, T. Gut hormones such as amylin and GLP-1 in the control of eating and energy expenditure. Int J Obes Supp 6 (Suppl 1), S15–S21 (2016). https://doi.org/10.1038/ijosup.2016.4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijosup.2016.4

This article is cited by

Search

Advanced search

Quick links