The receptive function of hypothalamic and brainstem centres to hormonal and nutrient signals affecting energy balance

Proceedings of the Nutrition Society

Volumn 71, Issue 4, 2012, Pages 463-477

  Riediger, Thomas ^a  

^a UNIVERSITY OF ZURICH   (Switzerland)

Author keywords

Arcuate nucleus; Area postrema; Food intake; Obesity

Indexed keywords

AMYLIN; AMYLIN RECEPTOR; CALCITONIN RECEPTOR; CARNITINE PALMITOYLTRANSFERASE I; EXENDIN 4; GHRELIN; GHRELIN RECEPTOR; GLUCAGON LIKE PEPTIDE 1; GLUCOSE; INSULIN; LEPTIN; LEPTIN RECEPTOR; MALONYL COENZYME A DECARBOXYLASE; MAMMALIAN TARGET OF RAPAMYCIN; MELANOCORTIN RECEPTOR; PEPTIDE YY; STAT3 PROTEIN;

ARCUATE NUCLEUS; AREA POSTREMA; BARIATRIC SURGERY; BLOOD BRAIN BARRIER; BODY WEIGHT; BRAIN STEM; CALORIC INTAKE; CONFERENCE PAPER; DEAFFERENTATION; ENERGY BALANCE; FATTY ACID OXIDATION; FOOD DEPRIVATION; FOOD INTAKE; GENE EXPRESSION; GENETIC MANIPULATION; GLUCONEOGENESIS; GLUCOSE METABOLISM; HUMAN; HYPERINSULINEMIA; HYPOTHALAMUS; IN VIVO STUDY; INSULIN RESISTANCE; LIPID METABOLISM; METABOLISM; OBESITY; PARABRACHIAL NUCLEUS; PHENOTYPE; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; WHITE ADIPOSE TISSUE;

ANIMALS; APPETITE; ARCUATE NUCLEUS; AREA POSTREMA; BARIATRIC SURGERY; ENERGY INTAKE; ENERGY METABOLISM; GASTROINTESTINAL HORMONES; HOMEOSTASIS; HUMANS; OBESITY; SIGNAL TRANSDUCTION; WEIGHT LOSS;

EID: 84868290228     PISSN: 00296651     EISSN: 14752719     Source Type: Journal    
DOI: 10.1017/S0029665112000778     Document Type: Conference Paper

References (165)

1. Ferchak CV & Meneghini LF (2004) Obesity, bariatric surgery and type 2 diabetes Y a systematic review. Diabetes Metab Res Rev 20, 438-445.
2. Ahn SM, Pomp A & Rubino F (2010) Metabolic surgery for type 2 diabetes. Ann N Y Acad Sci 1212, E37-E45.
3. Roth JD, Roland BL, Cole RL, et al. (2008) Leptin responsiveness restored by amylin agonism in diet-induced obesity: Evidence from nonclinical and clinical studies. Proc Natl Acad Sci USA 105, 7257-7262.
4. Turek VF, Trevaskis JL, Levin BE, et al. (2010) Mechanisms of amylin/leptin synergy in rodent models. Endocrinology 151, 143-152.
5. Zhang Y, Proenca R, Maffei M, et al. (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425-432.
6. Chua S, Chung W, Wu-Peng X, et al. (1996) Phenotypes of mouse diabetes and rat fatty due to mutations in the OB (leptin) receptor. Science 271, 994-996.
7. Broberger C, Johansen J, Johansson C, et al. (1998) The neuropeptide Y/agouti gene-related protein (AGRP) brain circuitry in normal, anorectic, and monosodium glutamatetreated mice. Proc Natl Acad Sci USA 95, 15043-15048.
8. Ellacott K & Cone R (2004) The central melanocortin system and the integration of short- and long-term regulators of energy homeostasis. Recent Prog Horm Res 59, 395-408.
9. Cowley M, Smart J, Rubinstein M, et al. (2001) Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 411, 480-484.
10. Spanswick D, Smith M, Groppi V, et al. (1997) Leptin inhibits hypothalamic neurons by activation of ATPsensitive potassium channels. Nature 390, 521-525.
11. Woods SC & Seeley RJ (2000) Adiposity signals and the control of energy homeostasis. Nutrition 16, 894-902.
12. Heymsfield SB, Greenberg AS, Fujioka K, et al. (1999) Recombinant leptin for weight loss in obese and lean adults: A randomized, controlled, dose-escalation trial. JAMA 282, 1568-1575.
13. Boden G, Chen X, Mozzoli M, et al. (1996) Effect of fasting on serum leptin in normal human subjects. J Clin Endocrinol Metab 81, 3419-3423.
14. Weigle DS, Duell PB, Connor WE, et al. (1997) Effect of fasting, refeeding, and dietary fat restriction on plasma leptin levels. J Clin Endocrinol Metab 82, 561-565.
15. Kojima M, Hosoda H, Date Y, et al. (1999) Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402, 656-660.
16. Tschop M, Smiley D & Heiman M (2000) Ghrelin induces adiposity in rodents. Nature 407, 908-913.
17. Asakawa A, Inui A, Kaga T, et al. (2001) Ghrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin. Gastroenterology 120, 337-345.
18. Shiiya T, Nakazato M, Mizuta M, et al. (2002) Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J Clin Endocrinol Metab 87, 240-244.
19. Traebert M, Riediger T, Whitebread S, et al. (2002) Ghrelin acts on leptin-responsive neurones in the rat arcuate nucleus. J Neuroendocrinol 14, 580-586.
20. Riediger T, Traebert M, Schmid HA, et al. (2003) Sitespecific effects of ghrelin on the neuronal activity in the hypothalamic arcuate nucleus. Neurosci Lett 341, 151-155.
21. Becskei C, Bilik KU, Klussmann S, et al. (2008) The antighrelin Spiegelmer NOX-B11-3 blocks ghrelin- but not fasting-induced neuronal activation in the hypothalamic arcuate nucleus. J Neuroendocrinol 20, 85-92.
22. Wang L, Saint-Pierre DH & Tache Y (2002) Peripheral ghrelin selectively increases Fos expression in neuropeptide Y Y synthesizing neurons in mouse hypothalamic arcuate nucleus. Neurosci Lett 325, 47-51.
23. Guan X, Yu H, Palyha O, et al. (1997) Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues. Brain Res Mol Brain Res 48, 23-29.
24. Willesen M, Kristensen P & Romer J (1999) Co-localization of growth hormone secretagogue receptor and NPY mRNA in the arcuate nucleus of the rat. Neuroendocrinology 70, 306-316.
25. Hewson AK, Viltart O, McKenzie DN, et al. (1999) GHRP-6-induced changes in electrical activity of single cells in the arcuate, ventromedial and periventricular nucleus neurones [correction of nuclei] of a hypothalamic slice preparation in vitro. J Neuroendocrinol 11, 919-923.
26. Salome N, Haage D, Perrissoud D, et al. (2009) Anorexigenic and electrophysiological actions of novel ghrelin receptor (GHS-R1A) antagonists in rats. Eur J Pharmacol 612, 167-173.
27. Tung YC, Hewson AK & Dickson SL (2001) Actions of leptin on growth hormone secretagogue-responsive neurones in the rat hypothalamic arcuate nucleus recorded in vitro. J Neuroendocrinol 13, 209-215.
28. Cowley MA, Smith RG, Diano S, et al. (2003) The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron 37, 649-661.
29. Dickson SL & Luckman SM (1997) Induction of c-Fos messenger ribonucleic acid in neuropeptide Y and growth hormone (GH)-releasing factor neurons in the rat arcuate nucleus following systemic injection of the GH secretagogue, GH-releasing peptide-6. Endocrinology 138, 771-777.
30. Geary N (2004) Endocrine controls of eating: CCK, leptin, and ghrelin. Physiol Behav 81, 719-733.
31. Kirchner H, Heppner KM & Tschop MH (2012) The role of ghrelin in the control of energy balance. Handb Exp Pharmacol, 161-184.
32. Cummings DE, Weigle DS, Frayo RS, et al. (2002) Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med 346, 1623-1630.
33. Dickson SL, Egecioglu E, Landgren S, et al. (2011) The role of the central ghrelin system in reward from food and chemical drugs. Mol Cell Endocrinol 340, 80-87.
34. Borg CM, le Roux CW, Ghatei MA, et al. (2006) Progressive rise in gut hormone levels after Roux-en-Y gastric bypass suggests gut adaptation and explains altered satiety. Br J Surg 93, 210-215.
35. le Roux CW, Aylwin SJ, Batterham RL, et al. (2006) Gut hormone profiles following bariatric surgery favor an anorectic state, facilitate weight loss, and improve metabolic parameters. Ann Surg 243, 108-114.
36. le Roux CW, Welbourn R, Werling M, et al. (2007) Gut hormones as mediators of appetite and weight loss after Roux-en-Y gastric bypass. Ann Surg 246, 780-785.
37. Chandarana K, Gelegen C, Karra E, et al. (2011) Diet and gastrointestinal bypass-induced weight loss: The roles of ghrelin and peptide YY. Diabetes 60, 810-818.
38. Grandt D, Schimiczek M, Beglinger C, et al. (1994) Two molecular forms of peptide YY (PYY) are abundant in human blood: Characterization of a radioimmunoassay recognizing PYY 1-36 and PYY 3-36. Regul Pept 51, 151-159.
39. Dumont Y, Fournier A, St-Pierre S, et al. (1995) Characterization of neuropeptide Y binding sites in rat brain membrane preparations using [125I][Leu31,Pro34]peptide YY and [125I]peptide YY3-36 as selective Y1 and Y2 radioligands. J Pharmacol Exp Ther 272, 673-680.
40. Degen L, Oesch S, Casanova M, et al. (2005) Effect of peptide YY3-36 on food intake in humans. Gastroenterology 129, 1430-1436.
41. Sloth B, Holst JJ, Flint A, et al. (2007) Effects of PYY1-36 and PYY3-36 on appetite, energy intake, energy expenditure, glucose and fat metabolism in obese and lean subjects. Am J Physiol Endocrinol Metab 292, E1062-E1068.
42. Batterham RL, Cowley MA, Small CJ, et al. (2002) Gut hormone PYY(3-36) physiologically inhibits food intake. Nature 418, 650-654.
43. Ghamari-Langroudi M, Colmers WF & Cone RD (2005) PYY3-36 inhibits the action potential firing activity of POMC neurons of arcuate nucleus through postsynaptic Y2 receptors. Cell Metab 2, 191-199.
44. Riediger T, Bothe C, Becskei C, et al. (2004) Peptide YY directly inhibits ghrelin-activated neurons of the arcuate nucleus and reverses fasting-induced c-Fos expression. Neuroendocrinology 79, 317-326.
45. Batterham RL, Cohen MA, Ellis SM, et al. (2003) Inhibition of food intake in obese subjects by peptide YY3-36. N Engl J Med 349, 941-948.
46. Adams SH, Lei C, Jodka CM, et al. (2006) PYY[3-36] administration decreases the respiratory quotient and reduces adiposity in diet-induced obese mice. J Nutr 136, 195-201.
47. Koegler FH, Enriori PJ, Billes SK, et al. (2005) Peptide YY(3-36) inhibits morning, but not evening, food intake and decreases body weight in rhesus macaques. Diabetes 54, 3198-3204.
48. Talsania T, Anini Y, Siu S, et al. (2005) Peripheral exendin-4 and peptide YY(3-36) synergistically reduce food intake through different mechanisms in mice. Endocrinology 146, 3748-3756.
49. Roth JD, Coffey T, Jodka CM, et al. (2007) Combination therapy with amylin and peptide YY[3-36] in obese rodents: Anorexigenic synergy and weight loss additivity. Endocrinology 148, 6054-6061.
50. Orskov C, Wettergren A & Holst JJ (1996) Secretion of the incretin hormones glucagon-like peptide-1 and gastric inhibitory polypeptide correlates with insulin secretion in normal man throughout the day. Scand J Gastroenterol 31, 665-670.
51. Kreymann B, Williams G, Ghatei MA, et al. (1987) Glucagon-like peptide-1 7-36: A physiological incretin in man. Lancet 2, 1300-1304.
52. Holst JJ (2007) The physiology of glucagon-like peptide 1. Physiol Rev 87, 1409-1439.
53. Larsen PJ, Tang-Christensen M, Holst JJ, et al. (1997) Distribution of glucagon-like peptide-1 and other preproglucagon-derived peptides in the rat hypothalamus and brainstem. Neuroscience 77, 257-270.
54. Merchenthaler I, Lane M & Shughrue P (1999) Distribution of pre-pro-glucagon and glucagon-like peptide-1 receptor messenger RNAs in the rat central nervous system. J Comp Neurol 403, 261-280.
55. Alvarez E, Roncero I, Chowen JA, et al. (1996) Expression of the glucagon-like peptide-1 receptor gene in rat brain. J Neurochem 66, 920-927.
56. Turton MD, O'Shea D, Gunn I, et al. (1996) A role for glucagon-like peptide-1 in the central regulation of feeding. Nature 379, 69-72.
57. Rodriquez de Fonseca F, Navarro M, Alvarez E, et al. (2000) Peripheral versus central effects of glucagon-like peptide-1 receptor agonists on satiety and body weight loss in Zucker obese rats. Metab Clin Exp 49, 709-717.
58. Dakin CL, Small CJ, Batterham RL, et al. (2004) Peripheral oxyntomodulin reduces food intake and body weight gain in rats. Endocrinology 145, 2687-2695.
59. Reidelberger RD, Haver AC, Apenteng BA, et al. (2011) Effects of exendin-4 alone and with peptide YY(3-36) on food intake and body weight in diet-induced obese rats. Obesity (Silver Spring) 19, 121-127.
60. Verdich C, Flint A, Gutzwiller JP, et al. (2001) A metaanalysis of the effect of glucagon-like peptide-1 (7-36) amide on ad libitum energy intake in humans. J Clin Endocrinol Metab 86, 4382-4389.
61. Ruttimann EB, Arnold M, Hillebrand JJ, et al. (2009) Intrameal hepatic portal and intraperitoneal infusions of glucagon-like peptide-1 reduce spontaneous meal size in the rat via different mechanisms. Endocrinology 150, 1174-1181.
62. Punjabi M, Arnold M, Geary N, et al. (2011) Peripheral glucagon-like peptide-1 (GLP-1) and satiation. Physiol Behav 105, 71-76.
63. Le Quellec A, Kervran A, Blache P, et al. (1992) Oxyntomodulin-like immunoreactivity: Diurnal profile of a new potential enterogastrone. J Clin Endocrinol Metab 74, 1405-1409.
64. Baggio LL, Huang Q, Brown TJ, et al. (2004) Oxyntomodulin and glucagon-like peptide-1 differentially regulate murine food intake and energy expenditure. Gastroenterology 127, 546-558.
65. Sandoval DA, Bagnol D, Woods SC, et al. (2008) Arcuate glucagon-like peptide 1 receptors regulate glucose homeostasis but not food intake. Diabetes 57, 2046-2054.
66. Dakin CL, Gunn I, Small CJ, et al. (2001) Oxyntomodulin inhibits food intake in the rat. Endocrinology 142, 4244-4250.
67. Riediger T, Eisele N, Scheel C, et al. (2010) Effects of glucagon-like peptide 1 and oxyntomodulin on neuronal activity of ghrelin-sensitive neurons in the hypothalamic arcuate nucleus. Am J Physiol Regul Integr Comp Physiol 298, R1061-R1067.
68. Klonoff DC, Buse JB, Nielsen LL, et al. (2008) Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years. Curr Med Res Opin 24, 275-286.
69. Rosenstock J, Klaff LJ, Schwartz S, et al. (2010) Effects of exenatide and lifestyle modification on body weight and glucose tolerance in obese subjects with and without prediabetes. Diabetes Care 33, 1173-1175.
70. Vilsboll T, Christensen M, Junker AE, et al. (2012) Effects of glucagon-like peptide-1 receptor agonists on weight loss: Systematic review and meta-analyses of randomised controlled trials. BMJ 344, d7771.
71. Schwartz MW, Woods SC, Porte D Jr, et al. (2000) Central nervous system control of food intake. Nature 404, 661-671.
72. Wang L, Martinez V, Barrachina MD, et al. (1998) Fos expression in the brain induced by peripheral injection of CCK or leptin plus CCK in fasted lean mice. Brain Res 791, 157-166.
73. Ueyama E, Morikawa Y, Yasuda T, et al. (2004) Attenuation of fasting-induced phosphorylation of mitogenactivated protein kinases (ERK/p38) in the mouse hypothalamus in response to refeeding. Neurosci Lett 371, 40-44.
74. Mistry AM, Helferich W & Romsos DR (1994) Elevated neuronal c-Fos-like immunoreactivity and messenger ribonucleic acid (mRNA) in genetically obese (ob/ob) mice. Brain Res 666, 53-60.
75. Becskei C, Lutz TA & Riediger T (2009) Diet-derived nutrients mediate the inhibition of hypothalamic NPY neurons in the arcuate nucleus of mice during refeeding. Am J Physiol Regul Integr Comp Physiol 297, R100-R110.
76. Coppola A, Liu ZW, Andrews ZB, et al. (2007) A central thermogenic-like mechanism in feeding regulation: An interplay between arcuate nucleus T3 and UCP2. Cell Metab 5, 21-33.
77. Sanchez E, Singru PS, Acharya R, et al. (2008) Differential effects of refeeding on melanocortin-responsive neurons in the hypothalamic paraventricular nucleus. Endocrinology 149, 4329-4335.
78. Singru PS, Sanchez E, Fekete C, et al. (2007) Importance of melanocortin signaling in refeeding-induced neuronal activation and satiety. Endocrinology 148, 638-646.
79. Wang R, Liu X, Hentges ST, et al. (2004) The regulation of glucose-excited neurons in the hypothalamic arcuate nucleus by glucose and feeding-relevant peptides. Diabetes 53, 1959-1965.
80. Fioramonti X, Contie S, Song Z, et al. (2007) Characterization of glucosensing neuron subpopulations in the arcuate nucleus: Integration in neuropeptide Y and pro-opio melanocortin networks? Diabetes 56, 1219-1227.
81. Muroya S, Yada T, Shioda S, et al. (1999) Glucosesensitive neurons in the rat arcuate nucleus contain neuropeptide Y. Neurosci Lett 264, 113-116.
82. Claret M, Smith MA, Batterham RL, et al. (2007) AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons. J Clin Invest 117, 2325-2336.
83. Parton LE, Ye CP, Coppari R, et al. (2007) Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity. Nature 449, 228-232.
84. Miki T, Liss B, Minami K, et al. (2001) ATP-sensitive K+ channels in the hypothalamus are essential for the maintenance of glucose homeostasis. Nat Neurosci 4, 507-512.
85. Levin BE, Routh VH, Kang L, et al. (2004) Neuronal glucosensing: What do we know after 50 years? Diabetes 53, 2521-2528.
86. Kahn BB, Alquier T, Carling D, et al. (2005) AMPactivated protein kinase: Ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab 1, 15-25.
87. Minokoshi Y, Alquier T, Furukawa N, et al. (2004) AMPkinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature 428, 569-574.
88. Becskei C, Lutz TA & Riediger T (2008) Glucose reverses fasting-induced activation in the arcuate nucleus of mice. Neuroreport 19, 105-109.
89. Morgan K, Obici S & Rossetti L (2004) Hypothalamic responses to long-chain fatty acids are nutritionally regulated. J Biol Chem 279, 31139-31148.
90. Obici S, Feng Z, Morgan K, et al. (2002) Central administration of oleic acid inhibits glucose production and food intake. Diabetes 51, 271-275.
91. Wang R, Cruciani-Guglielmacci C, Migrenne S, et al. (2006) Effects of oleic acid on distinct populations of neurons in the hypothalamic arcuate nucleus are dependent on extracellular glucose levels. J Neurophysiol 95, 1491-1498.
92. Jo YH, Su Y, Gutierrez-Juarez R, et al. (2009) Oleic acid directly regulates POMC neuron excitability in the hypothalamus. J Neurophysiol 101, 2305-2316.
93. Loftus TM, Jaworsky DE, Frehywot GL, et al. (2000) Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors. Science 288, 2379-2381.
94. Kim EK, Miller I, Landree LE, et al. (2002) Expression of FAS within hypothalamic neurons: A model for decreased food intake after C75 treatment. Am J Physiol Endocrinol Metab 283, E867-E879.
95. Miller I, Ronnett GV, Moran TH, et al. (2004) Anorexigenic C75 alters c-Fos in mouse hypothalamic and hindbrain subnuclei. Neuroreport 15, 925-929.
96. He W, Lam TK, Obici S, et al. (2006) Molecular disruption of hypothalamic nutrient sensing induces obesity. Nat Neurosci 9, 227-233.
97. Obici S, Feng Z, Arduini A, et al. (2003) Inhibition of hypothalamic carnitine palmitoyltransferase-1 decreases food intake and glucose production. Nat Med 9, 756-761.
98. Jacinto E & Hall MN (2003) Tor signalling in bugs, brain and brawn. Nat Rev Mol Cell Biol 4, 117-126.
99. Cota D, Proulx K, Smith KA, et al. (2006) Hypothalamic mTOR signaling regulates food intake. Science 312, 927-930.
100. Blouet C, Jo YH, Li X, et al. (2009) Mediobasal hypothalamic leucine sensing regulates food intake through activation of a hypothalamus-brainstem circuit. J Neurosci 29, 8302-8311.
101. Bagnasco M, Tulipano G, Melis MR, et al. (2003) Endogenous ghrelin is an orexigenic peptide acting in the arcuate nucleus in response to fasting. Regul Pept 111, 161-167.
102. Helmling S, Maasch C, Eulberg D, et al. (2004) Inhibition of ghrelin action in vitro and in vivo by an RNA-Spiegelmer. Proc Natl Acad Sci USA 101, 13174-13179.
103. Kobelt P, Helmling S, Stengel A, et al. (2006) Antighrelin Spiegelmer NOX-B11 inhibits neurostimulatory and orexigenic effects of peripheral ghrelin in rats. Gut 55, 788-792.
104. Becskei C, Lutz TA & Riediger T (2010) Reduced fastinginduced activation of hypothalamic arcuate neurons is associated with hyperleptinemia and increased leptin sensitivity in obese mice. Am J Physiol Regul Integr Comp Physiol 299, R632-R641.
105. Riediger T, Michel S, Becskei C, et al. (2007) Diet-derived nutrients and PYY modulate the effects of amylin on c-Fos expression in the area postrema and on food intake. 2007 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2010. Online. Program No. 299.7/UU3.
106. Halaas JL, Boozer C, Blair-West J, et al. (1997) Physiological response to long-term peripheral and central leptin infusion in lean and obese mice. Proc Natl Acad Sci USA 94, 8878-8883.
107. Bjorntorp P (1997) Body fat distribution, insulin resistance, and metabolic diseases. Nutrition 13, 795-803.
108. Munzberg H, Flier JS & Bjorbaek C (2004) Region-specific leptin resistance within the hypothalamus of diet-induced obese mice. Endocrinology 145, 4880-4889.
109. Gamber KM, Huo L, Ha S, et al. (2012) Over-expression of leptin receptors in hypothalamic POMC neurons increases susceptibility to diet-induced obesity. PLoS One 7, e30485.
110. Enriori PJ, Evans AE, Sinnayah P, et al. (2007) Diet-induced obesity causes severe but reversible leptin resistance in arcuate melanocortin neurons. Cell Metab 5, 181-194.
111. Briggs DI, Enriori PJ, Lemus MB, et al. (2010) Dietinduced obesity causes ghrelin resistance in arcuate NPY/AgRP neurons. Endocrinology 151, 4745-4755.
112. Levin BE, Govek EK & Dunn-Meynell AA (1998) Reduced glucose-induced neuronal activation in the hypothalamus of diet-induced obese rats. Brain Res 808, 317-319.
113. Becskei C, Lutz TA & Riediger T (2009) Blunted fastinginduced hypothalamic activation and refeeding hyperphagia in late-onset obesity. Neuroendocrinology 90, 371-382.
114. Banks WA & Farrell CL (2003) Impaired transport of leptin across the blood-brain barrier in obesity is acquired and reversible. Am J Physiol Endocrinol Metab 285, E10-E15.
115. Banks WA, Coon AB, Robinson SM, et al. (2004) Triglycerides induce leptin resistance at the blood-brain barrier. Diabetes 53, 1253-1260.
116. Baskin DG, Breininger JF & Schwartz MW (2000) SOCS-3 expression in leptin-sensitive neurons of the hypothalamus of fed and fasted rats. Regul Pept 92, 9-15.
117. Morrison CD, White CL, Wang Z, et al. (2007) Increased hypothalamic protein tyrosine phosphatase 1B contributes to leptin resistance with age. Endocrinology 148, 433-440.
118. Baskin DG, Seeley RJ, Kuijper JL, et al. (1998) Increased expression of mRNA for the long form of the leptin receptor in the hypothalamus is associated with leptin hypersensitivity and fasting. Diabetes 47, 538-543.
119. Baskin DG, Breininger JF, Bonigut S, et al. (1999) Leptin binding in the arcuate nucleus is increased during fasting. Brain Res 828, 154-158.
120. van der Kooy D & Koda LY (1983) Organization of the projections of a circumventricular organ: The area postrema in the rat. J Comp Neurol 219, 328-338.
121. Ritter S, McGlone JJ & Kelley KW (1980) Absence of lithium-induced taste aversion after area postrema lesion. Brain Res 201, 501-506.
122. Hyde TM & Miselis RR (1983) Effects of area postrema/caudal medial nucleus of solitary tract lesions on food intake and body weight. Am J Physiol Regul Integr Comp Physiol 244, R577-R587.
123. Miselis RR, Hyde TM & Shapiro RE (1984) Area postrema and adjacent solitary nucleus in water and energy balance. Fed Proc 43, 2969-2971.
124. Bird E, Cardone CC & Contreras RJ (1983) Area postrema lesions disrupt food intake induced by cerebroventricular infusions of 5-thioglucose in the rat. Brain Res 270, 193-196.
125. Young A (2005) Tissue expression and secretion of amylin. Adv Pharmacol 52, 19-45.
126. Lutz TA, Del Prete E & Scharrer E (1994) Reduction of food intake in rats by intraperitoneal injection of low doses of amylin. Physiol Behav 55, 891-895.
127. Lutz TA, Geary N, Szabady MM, et al. (1995) Amylin decreases meal size in rats. Physiol Behav 58, 1197-1202.
128. Arnelo U, Reidelberger R, Adrian TE, et al. (1998) Sufficiency of postprandial plasma levels of islet amyloid polypeptide for suppression of feeding in rats. Am J Physiol Regul Integr Comp Physiol 275, R1537-R1542.
129. Reidelberger RD, Haver AC, Arnelo U, et al. (2004) Amylin receptor blockade stimulates food intake in rats. Am J Physiol Regul Integr Comp Physiol 287, R568-R574.
130. Lutz TA, Del Prete E & Scharrer E (1995) Subdiaphragmatic vagotomy does not influence the anorectic effect of amylin. Peptides 16, 457-462.
131. Lutz TA, Mollet A, Rushing PA, et al. (2001) The anorectic effect of a chronic peripheral infusion of amylin is abolished in area postrema/nucleus of the solitary tract (AP/TS) lesioned rats. Int J Obes Relat Metab Disord 25, 1005-1011.
132. Lutz TA, Senn M, Althaus J, et al. (1998) 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 19, 309-317.
133. Mack CM, Soares CJ, Wilson JK, et al. (2010) Davalintide (AC2307), a novel amylin-mimetic peptide: Enhanced pharmacological properties over native amylin to reduce food intake and body weight. Int J Obes (Lond) 34, 385-395.
134. Christopoulos G, Perry KJ, Morfis M, et al. (1999) Multiple amylin receptors arise from receptor activity-modifying protein interaction with the calcitonin receptor gene product. Mol Pharmacol 56, 235-242.
135. Becskei C, Riediger T, Zund D, et al. (2004) Immunohistochemical mapping of calcitonin receptors in the adult rat brain. Brain Res 1030, 221-233.
136. Barth SW, Riediger T, Lutz TA, et al. (2004) Peripheral amylin activates circumventricular organs expressing calcitonin receptor a/b subtypes and receptor-activity modifying proteins in the rat. Brain Res 997, 97-102.
137. Riediger T, Schmid HA, Lutz T, et al. (2001) Amylin potently activates AP neurons possibly via formation of the excitatory second messenger cGMP. Am J Physiol Regul Integr Comp Physiol 281, R1833-R1843.
138. Rowland NE, Crews EC & Gentry RM (1997) Comparison of Fos induced in rat brain by GLP-1 and amylin. Regul Pept 71, 171-174.
139. Riediger T, Zuend D, Becskei C, et al. (2004) 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 286, R114-R122.
140. Potes CS, Turek VF, Cole RL, et al. (2010) Noradrenergic neurons of the area postrema mediate amylin's hypophagic action. Am J Physiol Regul Integr Comp Physiol 299, R623-R631.
141. Funahashi M & Adachi A (1993) Glucose-responsive neurons exist within the area postrema of the rat: In vitro study on the isolated slice preparation. Brain Res Bull 32, 531-535.
142. Riediger T, Schmid HA, Lutz TA, et al. (2002) Amylin and glucose co-activate area postrema neurons of the rat. Neurosci Lett 328, 121-124.
143. Ritter S, Dinh TT & Zhang Y (2000) Localization of hindbrain glucoreceptive sites controlling food intake and blood glucose. Brain Res 856, 37-47.
144. Schvarcz E, Palmer M, Aman J, et al. (1995) Hypoglycemia increases the gastric emptying rate in healthy subjects. Diabetes Care 18, 674-676.
145. Gedulin BR & Young AA (1998) Hypoglycemia overrides amylin-mediated regulation of gastric emptying in rats. Diabetes 47, 93-97.
146. Young A (2005) Inhibition of gastric emptying. Adv Pharmacol 52, 99-121.
147. Young AA (2012) Brainstem sensing of meal-related signals in energy homeostasis. Neuropharmacology 63, 31-45.
148. Michel S, Becskei C, Erguven E, et al. (2007) Diet-derived nutrients modulate the effects of amylin on c-Fos expression in the area postrema and on food intake. Neuroendocrinology 86, 124-135.
149. Züger D, Forster K, Lutz TA, et al. (2011) The sensitivity of AP neurons to amylin and GLP-1 is modulated by the feeding status. Appetite 57, Suppl. 1, S48-S49.
150. Ritter S & Taylor JS (1990) Vagal sensory neurons are required for lipoprivic but not glucoprivic feeding in rats. Am J Physiol Regul Integr Comp Physiol 258, R1395-R1401.
151. Monnikes H, Lauer G, Bauer C, et al. (1997) Pathways of Fos expression in locus ceruleus, dorsal vagal complex, and PVN in response to intestinal lipid. Am J Physiol Regul Integr Comp Physiol 273, R2059-R2071.
152. Bhavsar S, Watkins J & Young A (1998) Synergy between amylin and cholecystokinin for inhibition of food intake in mice. Physiol Behav 64, 557-561.
153. Boyle CN, Rossier MM & Lutz TA (2011) Influence of high-fat feeding, diet-induced obesity, and hyperamylinemia on the sensitivity to acute amylin. Physiol Behav 104, 20-28.
154. Potes CS, Lutz TA & Riediger T (2010) Identification of central projections from amylin-activated neurons to the lateral hypothalamus. Brain Res 1334, 31-44.
155. Roth JD, Trevaskis JL, Turek VF, et al. (2010) "Weighing in" on synergy: Preclinical research on neurohormonal antiobesity combinations. Brain Res 1350, 86-94.
156. Baraboi ED, Michel C, Smith P, et al. (2010) Effects of albumin-conjugated PYY on food intake: The respective roles of the circumventricular organs and vagus nerve. Eur J Neurosci 32, 826-839.
157. Cox JE & Randich A (2004) Enhancement of feeding suppression by PYY(3-36) in rats with area postrema ablations. Peptides 25, 985-989.
158. Deng X, Guarita DR, Pedroso MR, et al. (2001) Area postrema lesion alters the effects of peptide YY on 2-DG-stimulated pancreatic exocrine secretion. Dig Dis Sci 46, 2460-2469.
159. Dumont Y, Fournier A, St-Pierre S, et al. (1996) Autoradiographic distribution of [125I]Leu31,Pro34]PYY and [125I]PYY3-36 binding sites in the rat brain evaluated with two newly developed Y1 and Y2 receptor radioligands. Synapse 22, 139-158.
160. Dumont Y, Fournier A & Quirion R (1998) Expression and characterization of the neuropeptide Y Y5 receptor subtype in the rat brain. J Neurosci 18, 5565-5574.
161. Dumont Y, Moyse E, Fournier A, et al. (2007) Distribution of peripherally injected peptide YY ([125I] PYY (3-36)) and pancreatic polypeptide ([125I] hPP) in the CNS: Enrichment in the area postrema. J Mol Neurosci 33, 294-304.
162. Bello NT, Kemm MH, Ofeldt EM, et al. (2010) 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 299, R945-R952.
163. Pacheco-López G, Punjabi M, Graber M, et al. (2010) Hindbrain glucagon-like peptide-1 receptors (GLP-1R) mediate the eating-inhibitory effect of hepatic portal vein (HPV) GLP-1 infusions. Appetite 54, 668.
164. Baraboi ED, Smith P, Ferguson AV, et al. (2010) Lesions of area postrema and subfornical organ alter exendin-4-induced brain activation without preventing the hypophagic effect of the GLP-1 receptor agonist. Am J Physiol Regul Integr Comp Physiol 298, R1098-R1110.
165. Thiele TE, Seeley RJ, D'Alessio D, et al. (1998) Central infusion of glucagon-like peptide-1-(7-36) amide (GLP-1) receptor antagonist attenuates lithium chlorideinduced c-Fos induction in rat brainstem. Brain Res 801, 164-170.