What is a chemical messengers secreted by fat cells that acts as an appetite suppressant?

1. Popkin BM, Adair LS, Ng SW. Global nutrition transition and the pandemic of obesity in developing countries. Nutr Rev. 2012;70:3-21. [PMC free article] [PubMed] [Google Scholar]

2. Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011-2012. JAMA. 2014;311:806-814. [PMC free article] [PubMed] [Google Scholar]

3. Wang YC, McPherson K, Marsh T, Gortmaker SL, Brown M. Health and economic burden of the projected obesity trends in the USA and the UK. Lancet. 2011;378:815-825. [PubMed] [Google Scholar]

4. Kolotkin RL, Meter K, Williams GR. Quality of life and obesity. Obes Rev. 2001;2:219-229. [PubMed] [Google Scholar]

5. Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. Circulation. 2014;129(25 suppl 2):S102-S138. doi: 10.1161/01.cir.0000437739.71477.ee. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

6. Sjostrom L. Review of the key results from the Swedish Obese Subjects (SOS) trial: a prospective controlled intervention study of bariatric surgery. J Intern Med. 2013;273:219-234. [PubMed] [Google Scholar]

7. Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. N Eng J Med. 1995;332:621-628. [PubMed] [Google Scholar]

8. Levitsky DA. The non-regulation of food intake in humans: hope for reversing the epidemic of obesity. Physiol Behav. 2005;86:623-632. [PubMed] [Google Scholar]

9. Levitsky DA. Putting behavior back into feeding behavior: a tribute to George Collier. Appetite. 2002;38:143-148. [PubMed] [Google Scholar]

10. Elmquist JK, Coppari R, Balthasar N, Ichinose M, Lowell BB. Identifying hypothalamic pathways controlling food intake, body weight, and glucose homeostasis. J Comp Neurol. 2005;493:63-71. [PubMed] [Google Scholar]

11. Flier JS. Obesity wars: molecular progress confronts an expanding epidemic. Cell. 2004;116:337-350. [PubMed] [Google Scholar]

12. Seeley RJ, Woods SC. Monitoring of stored and available fuel by the CNS: implications for obesity. Nat Rev Neurosci. 2003;4:901-909. [PubMed] [Google Scholar]

13. Woods SC. The control of food intake: behavioral versus molecular perspectives. Cell Metab. 2009;9:489-498. [PMC free article] [PubMed] [Google Scholar]

14. Stellar E. The physiology of motivation. Psychol Rev. 1954;61:5-22. [PubMed] [Google Scholar]

15. Anand BK, Brobeck JR. Hypothalamic control of food intake in rats and cats. Yale J Biol Med. 1951;24:123-140. [PMC free article] [PubMed] [Google Scholar]

16. Orskov C, Poulsen SS, Møller M, Holst JJ. Glucagon-like peptide I receptors in the subfornical organ and the area postrema are accessible to circulating glucagon-like peptide I. Diabetes. 1996;45:832-835. [PubMed] [Google Scholar]

17. Shapiro RE, Miselis RR. The central neural connections of the area postrema of the rat. J Comp Neurol. 1985;234:344-364. [PubMed] [Google Scholar]

18. Renner E, Puskás N, Dobolyi A, Palkovits M. Glucagon-like peptide-1 of brainstem origin activates dorsomedial hypothalamic neurons in satiated rats. Peptides. 2012;35:14-22. [PubMed] [Google Scholar]

19. Puskás N, Papp RS, Gallatz K, Palkovits M. Interactions between orexin-immunoreactive fibers and adrenaline or noradrenaline-expressing neurons of the lower brainstem in rats and mice. Peptides. 2010;31:1589-1597. [PubMed] [Google Scholar]

20. Ricardo JA, Koh ET. Anatomical evidence of direct projections from the nucleus of the solitary tract to the hypothalamus, amygdala, and other forebrain structures in the rat. Brain Res. 1978;153:1-26. [PubMed] [Google Scholar]

21. Schwartz MW, Porte D. Diabetes, obesity, and the brain. Science. 2005;307:375-379. [PubMed] [Google Scholar]

22. Woods SC, Seeley RJ, Porte D, Schwartz MW. Signals that regulate food intake and energy homeostasis. Science. 1998;280:1378-1383. [PubMed] [Google Scholar]

23. Fan W, Boston BA, Kesterson RA, Hruby VJ, Cone RD. Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature. 1997;385:165-168. [PubMed] [Google Scholar]

24. Park JH, Lee MJ, Song MY, Bose S, Shin BC, Kim HJ. Efficacy and safety of mixed oriental herbal medicines for treating human obesity: a systematic review of randomized clinical trials. J Med Food. 2012;15:589-597. [PubMed] [Google Scholar]

25. Mountjoy KG. Functions for pro-opiomelanocortin-derived peptides in obesity and diabetes. Biochem J. 2010;428:305-324. [PubMed] [Google Scholar]

26. Pritchard LE, Turnbull AV, White A. Pro-opiomelanocortin processing in the hypothalamus: impact on melanocortin signalling and obesity. J Endocrinol. 2002;172:411-421. [PubMed] [Google Scholar]

27. Gantz I, Miwa H, Konda Y, et al. Molecular cloning, expression, and gene localization of a fourth melanocortin receptor. J Biol Chem. 1993;268:15174-15179. [PubMed] [Google Scholar]

28. Kishi T, Aschkenasi CJ, Lee CE, Mountjoy KG, Saper CB, Elmquist JK. Expression of melanocortin 4 receptor mRNA in the central nervous system of the rat. J Comp Neurol. 2003;457:213-235. [PubMed] [Google Scholar]

29. Näslund E, Hellström PM. Appetite signaling: from gut peptides and enteric nerves to brain. Physiol Behav. 2007;92:256-262. [PubMed] [Google Scholar]

30. Williams KW, Scott MM, Elmquist JK. Modulation of the central melanocortin system by leptin, insulin, and serotonin: coordinated actions in a dispersed neuronal network. Eur J Pharmacol. 2011;660:2-12. [PMC free article] [PubMed] [Google Scholar]

31. Farooqi IS, Keogh JM, Yeo GSH, Lank EJ, Cheetham T, O’Rahilly S. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med. 2003;348:1085-1095. [PubMed] [Google Scholar]

32. Rossi J, Balthasar N, Olson D, et al. Melanocortin-4 receptors expressed by cholinergic neurons regulate energy balance and glucose homeostasis. Cell Metab. 2011;13:195-204. [PMC free article] [PubMed] [Google Scholar]

33. Huszar D, Lynch CA, Fairchild-Huntress V, et al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell. 1997;88:131-141. [PubMed] [Google Scholar]

34. Lindqvist A, Baelemans A, Erlanson-Albertsson C. Effects of sucrose, glucose and fructose on peripheral and central appetite signals. Regul Pept. 2008;150:26-32. [PubMed] [Google Scholar]

35. Butler AA, Kesterson RA, Khong K, et al. A unique metabolic syndrome causes obesity in the melanocortin-3 receptor-deficient mouse. Endocrinology. 2000;141:3518-3521. [PubMed] [Google Scholar]

36. Sutton GM, Trevaskis JL, Hulver MW, et al. Diet-genotype interactions in the development of the obese, insulin-resistant phenotype of C57BL/6J mice lacking melanocortin-3 or -4 receptors. Endocrinology. 2006;147:2183-2196. [PMC free article] [PubMed] [Google Scholar]

37. Butler AA, Marks DL, Fan W, Kuhn CM, Bartolome M, Cone RD. Melanocortin-4 receptor is required for acute homeostatic responses to increased dietary fat. Nat Neurosci. 2001;4:605-611. [PubMed] [Google Scholar]

38. Farooqi IS, O’Rahilly S. Genetics of obesity in humans. Endocr Rev. 2006;27:710-718. [PubMed] [Google Scholar]

39. Barsh GS, Farooqi IS, O’Rahilly S. Genetics of body-weight regulation. Nature. 2000;404:644-651. [PubMed] [Google Scholar]

40. Yeo GSH, Heisler LK. Unraveling the brain regulation of appetite: lessons from genetics. Nat Neurosci. 2012;15:1343-1349. [PubMed] [Google Scholar]

41. Beck B. Neuropeptide Y in normal eating and in genetic and dietary-induced obesity. Philos Trans R Soc Lond B Biol Sci. 2006;361:1159-1185. [PMC free article] [PubMed] [Google Scholar]

42. Nijenhuis WA, Oosterom J, Adan RA. AgRP(83-132) acts as an inverse agonist on the human-melanocortin-4 receptor. Mol Endocrinol. 2001;15:164-171. [PubMed] [Google Scholar]

43. Kalra SP, Dube MG, Sahu A, Phelps CP, Kalra PS. Neuropeptide Y secretion increases in the paraventricular nucleus in association with increased appetite for food. Proc Natl Acad Sci U S A. 1991;88:10931-10935. [PMC free article] [PubMed] [Google Scholar]

44. Stanley BG, Kyrkouli SE, Lampert S, Leibowitz SF. Neuropeptide Y chronically injected into the hypothalamus: a powerful neurochemical inducer of hyperphagia and obesity. Peptides. 1986;7:1189-1192. [PubMed] [Google Scholar]

45. Srinivasan S, Lubrano-Berthelier C, Govaerts C, et al. Constitutive activity of the melanocortin-4 receptor is maintained by its N-terminal domain and plays a role in energy homeostasis in humans. J Clin Invest. 2004;114:1158-1164. [PMC free article] [PubMed] [Google Scholar]

46. Ollmann MM, Wilson BD, Yang YK, et al. Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein. Science. 1997;278:135-138. [PubMed] [Google Scholar]

47. Broberger C, Johansen J, Johansson C, Schalling M, Hökfelt T. The neuropeptide Y/agouti gene-related protein (AGRP) brain circuitry in normal, anorectic, and monosodium glutamate-treated mice. Proc Natl Acad Sci U S A. 1998;95:15043-15048. [PMC free article] [PubMed] [Google Scholar]

48. Hahn TM, Breininger JF, Baskin DG, Schwartz MW. Coexpression of Agrp and NPY in fasting-activated hypothalamic neurons. Nat Neurosci. 1998;1:271-272. [PubMed] [Google Scholar]

49. Xu B, Xie X. Neurotrophic factor control of satiety and body weight. Nat Rev Neurosci. 2016;17:282-292. [PMC free article] [PubMed] [Google Scholar]

50. Chen P, Li C, Haskell-Luevano C, Cone RD, Smith MS. Altered expression of agouti-related protein and its colocalization with neuropeptide Y in the arcuate nucleus of the hypothalamus during lactation. Endocrinology. 1999;140:2645-2650. [PubMed] [Google Scholar]

51. Maejima Y, Sedbazar U, Suyama S, et al. Nesfatin-1-regulated oxytocinergic signaling in the paraventricular nucleus causes anorexia through a leptin-independent melanocortin pathway. Cell Metab. 2009;10:355-365. [PubMed] [Google Scholar]

52. Arletti R, Benelli A, Bertolini A. Influence of oxytocin on feeding behavior in the rat. Peptides. 1989;10:89-93. [PubMed] [Google Scholar]

53. Renner E, Szabó-Meltzer KI, Puskás N, Tóth ZE, Dobolyi A, Palkovits M. Activation of neurons in the hypothalamic dorsomedial nucleus via hypothalamic projections of the nucleus of the solitary tract following refeeding of fasted rats. Eur J Neurosci. 2010;31:302-314. [PubMed] [Google Scholar]

54. Shimada M, Tritos NA, Lowell BB, Flier JS, Maratos-Flier E. Mice lacking melanin-concentrating hormone are hypophagic and lean. Nature. 1998;396:670-674. [PubMed] [Google Scholar]

55. Date Y, Ueta Y, Yamashita H, et al. Orexins, orexigenic hypothalamic peptides, interact with autonomic, neuroendocrine and neuroregulatory systems. Proc Natl Acad Sci U S A. 1999;96:748-753. [PMC free article] [PubMed] [Google Scholar]

56. Sakurai T, Amemiya A, Ishii M, et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell. 1998;92:573-585. [PubMed] [Google Scholar]

57. Aponte Y, Atasoy D, Sternson SM. AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training. Nat Neurosci. 2011;14:351-355. [PMC free article] [PubMed] [Google Scholar]

58. Wu Q, Palmiter RD. GABAergic signaling by AgRP neurons prevents anorexia via a melanocortin-independent mechanism. Eur J Pharmacol. 2011;660:21-27. [PMC free article] [PubMed] [Google Scholar]

59. Nonogaki K, Strack AM, Dallman MF, Tecott LH. Leptin-independent hyperphagia and type 2 diabetes in mice with a mutated serotonin 5-HT2C receptor gene. Nat Med. 1998;4:1152-1156. [PubMed] [Google Scholar]

60. Xu Y, Berglund ED, Sohn JW, et al. 5-HT2CRs expressed by pro-opiomelanocortin neurons regulate insulin sensitivity in liver. Nat Neurosci. 2010;13:1457-1459. [PMC free article] [PubMed] [Google Scholar]

61. Xu Y, Jones JE, Kohno D, et al. 5-HT2CRs expressed by pro-opiomelanocortin neurons regulate energy homeostasis. Neuron. 2008;60:582-589. [PMC free article] [PubMed] [Google Scholar]

62. Ho AJ, Raji CA, Becker JT, et al. Obesity is linked with lower brain volume in 700 AD and MCI patients. Neurobiol Aging. 2010;31:1326-1339. [PMC free article] [PubMed] [Google Scholar]

63. Deblon N, Veyrat-Durebex C, Bourgoin L, et al. Mechanisms of the anti-obesity effects of oxytocin in diet-induced obese rats. PLoS One. 2011;6:e25565. [PMC free article] [PubMed] [Google Scholar]

64. Maejima Y, Iwasaki Y, Yamahara Y, Kodaira M, Sedbazar U, Yada T. Peripheral oxytocin treatment ameliorates obesity by reducing food intake and visceral fat mass. Aging (Albany NY). 2011;3:1169-1177. [PMC free article] [PubMed] [Google Scholar]

65. Morton GJ, Thatcher BS, Reidelberger RD, et al. Peripheral oxytocin suppresses food intake and causes weight loss in diet-induced obese rats. Am J Physiol Endocrinol Metab. 2012;302:E134-E144. [PMC free article] [PubMed] [Google Scholar]

66. Zhang G, Bai H, Zhang H, et al. Neuropeptide exocytosis involving synaptotagmin-4 and oxytocin in hypothalamic programming of body weight and energy balance. Neuron. 2011;69:523-535. [PMC free article] [PubMed] [Google Scholar]

67. Camerino C. Low sympathetic tone and obese phenotype in oxytocin-deficient mice. Obesity (Silver Spring). 2009;17:980-984. [PubMed] [Google Scholar]

68. Takayanagi Y, Kasahara Y, Onaka T, Takahashi N, Kawada T, Nishimori K. Oxytocin receptor-deficient mice developed late-onset obesity. Neuroreport. 2008;19:951-955. [PubMed] [Google Scholar]

69. Kublaoui BM, Gemelli T, Tolson KP, Wang Y, Zinn AR. Oxytocin deficiency mediates hyperphagic obesity of Sim1 haploinsufficient mice. Mol Endocrinol. 2008;22:1723-1734. [PMC free article] [PubMed] [Google Scholar]

70. Altirriba J, Poher AL, Caillon A, et al. Divergent effects of oxytocin treatment of obese diabetic mice on adiposity and diabetes. Endocrinology. 2014;155:4189-4201. [PubMed] [Google Scholar]

71. Zhang G, Cai D. Circadian intervention of obesity development via resting-stage feeding manipulation or oxytocin treatment. Am J Physiol Endocrinol Metab. 2011;301:E1004-E1012. [PMC free article] [PubMed] [Google Scholar]

72. Blevins JE, Thompson BW, Anekonda VT, et al. Chronic CNS oxytocin signaling preferentially induces fat loss in high-fat diet-fed rats by enhancing satiety responses and increasing lipid utilization. Am J Physiol Regul Integr Comp Physiol. 2016;310:R640-R658. [PMC free article] [PubMed] [Google Scholar]

73. Blevins JE, Graham JL, Morton GJ, et al. Chronic oxytocin administration inhibits food intake, increases energy expenditure, and produces weight loss in fructose-fed obese rhesus monkeys. Am J Physiol Regul Integr Comp Physiol. 2015;308:R431-R438. [PMC free article] [PubMed] [Google Scholar]

74. Blevins JE, Ho JM. Role of oxytocin signaling in the regulation of body weight. Rev Endocr Metab Disord. 2013;14:311-329. [PMC free article] [PubMed] [Google Scholar]

75. Rinaman L. Oxytocinergic inputs to the nucleus of the solitary tract and dorsal motor nucleus of the vagus in neonatal rats. J Comp Neurol. 1998;399:101-109. [PubMed] [Google Scholar]

76. Sawchenko PE, Swanson LW. Immunohistochemical identification of neurons in the paraventricular nucleus of the hypothalamus that project to the medulla or to the spinal cord in the rat. J Comp Neurol. 1982;205:260-272. [PubMed] [Google Scholar]

77. Vrang N, Larsen PJ, Kristensen P, Tang-Christensen M. Central administration of cocaine-amphetamine-regulated transcript activates hypothalamic neuroendocrine neurons in the rat. Endocrinology. 2000;141:794-801. [PubMed] [Google Scholar]

78. Peruzzo B, Pastor FE, Blázquez JL, et al. A second look at the barriers of the medial basal hypothalamus. Exp Brain Res. 2000;132:10-26. [PubMed] [Google Scholar]

79. Ciofi P. The arcuate nucleus as a circumventricular organ in the mouse. Neurosci Lett. 2011;487:187-190. [PubMed] [Google Scholar]

80. Rodríguez EM, Blázquez JL, Guerra M. The design of barriers in the hypothalamus allows the median eminence and the arcuate nucleus to enjoy private milieus: the former opens to the portal blood and the latter to the cerebrospinal fluid. Peptides. 2010;31:757-776. [PubMed] [Google Scholar]

81. Shaver SW, Pang JJ, Wainman DS, Wall KM, Gross PM. Morphology and function of capillary networks in subregions of the rat tuber cinereum. Cell Tissue Res. 1992;267:437-448. [PubMed] [Google Scholar]

83. Kennedy GC. The role of depot fat in the hypothalamic control of food intake in the rat. Proc R Soc Lond B Biol Sci. 1953;140:578-596. [PubMed] [Google Scholar]

84. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372:425-432. [PubMed] [Google Scholar]

85. Wisse BE, Campfield LA, Marliss EB, Morais JA, Tenenbaum R, Gougeon R. Effect of prolonged moderate and severe energy restriction and refeeding on plasma leptin concentrations in obese women. Am J Clin Nutr. 1999;70:321-330. [PubMed] [Google Scholar]

86. Goldstone AP, Brynes AE, Thomas EL, et al. Resting metabolic rate, plasma leptin concentrations, leptin receptor expression, and adipose tissue measured by whole-body magnetic resonance imaging in women with Prader-Willi syndrome. Am J Clin Nutr. 2002;75:468-475. [PubMed] [Google Scholar]

87. Cnop M, Landchild MJ, Vidal J, et al. The concurrent accumulation of intra-abdominal and subcutaneous fat explains the association between insulin resistance and plasma leptin concentrations: distinct metabolic effects of two fat compartments. Diabetes. 2002;51:1005-1015. [PubMed] [Google Scholar]

88. Lammert A, Kiess W, Bottner A, Glasow A, Kratzsch J. Soluble leptin receptor represents the main leptin binding activity in human blood. Biochem Biophys Res Commun. 2001;283:982-988. [PubMed] [Google Scholar]

89. Yang G, Ge H, Boucher A, Yu X, Li C. Modulation of direct leptin signaling by soluble leptin receptor. Mol Endocrinol. 2004;18:1354-1362. [PubMed] [Google Scholar]

90. Schaab M, Kausch H, Klammt J, et al. Novel regulatory mechanisms for generation of the soluble leptin receptor: implications for leptin action. PLoS One. 2012;7:e34787. [PMC free article] [PubMed] [Google Scholar]

91. Schaab M, Kratzsch J. The soluble leptin receptor. Best Pract Res Clin Endocrinol Metab. 2015;29:661-670. [PubMed] [Google Scholar]

92. Tartaglia LA, Dembski M, Weng X, et al. Identification and expression cloning of a leptin receptor, OB-R. Cell. 1995;83:1263-1271. [PubMed] [Google Scholar]

93. Chen H, Charlat O, Tartaglia LA, et al. Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice. Cell. 1996;84:491-495. [PubMed] [Google Scholar]

94. Berglund ED, Vianna CR, Donato J, et al. Direct leptin action on POMC neurons regulates glucose homeostasis and hepatic insulin sensitivity in mice. J Clin Invest. 2012;122:1000-1009. [PMC free article] [PubMed] [Google Scholar]

95. Xu AW, Ste-Marie L, Kaelin CB, Barsh GS. Inactivation of signal transducer and activator of transcription 3 in proopiomelanocortin (pomc) neurons causes decreased pomc expression, mild obesity, and defects in compensatory refeeding. Endocrinology. 2007;148:72-80. [PubMed] [Google Scholar]

96. Bates SH, Stearns WH, Dundon TA, et al. STAT3 signalling is required for leptin regulation of energy balance but not reproduction. Nature. 2003;421:856-859. [PubMed] [Google Scholar]

97. Kwon O, Kim KW, Kim MS. Leptin signalling pathways in hypothalamic neurons. Cell Mol Life Sci. 2016;73:1457-1477. [PubMed] [Google Scholar]

98. Schwartz MW, Peskind E, Raskind M, Boyko EJ, Porte D. Cerebrospinal fluid leptin levels: relationship to plasma levels and to adiposity in humans. Nat Med. 1996;2:589-593. [PubMed] [Google Scholar]

99. Caro JF, Kolaczynski JW, Nyce MR, et al. Decreased cerebrospinal-fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance. Lancet. 1996;348:159-161. [PubMed] [Google Scholar]

100. Golden PL, Maccagnan TJ, Pardridge WM. Human blood-brain barrier leptin receptor. Binding and endocytosis in isolated human brain microvessels. J Clin Invest. 1997;99:14-18. [PMC free article] [PubMed] [Google Scholar]

101. Korner J, Chua SC, Williams JA, Leibel RL, Wardlaw SL. Regulation of hypothalamic proopiomelanocortin by leptin in lean and obese rats. Neuroendocrinology. 1999;70:377-383. [PubMed] [Google Scholar]

102. Lee SJ, Verma S, Simonds SE, et al. Leptin stimulates neuropeptide Y and cocaine amphetamine-regulated transcript coexpressing neuronal activity in the dorsomedial hypothalamus in diet-induced obese mice. J Neurosci. 2013;33:15306-15317. [PMC free article] [PubMed] [Google Scholar]

103. Meister B. Control of food intake via leptin receptors in the hypothalamus. Vitam Horm. 2000;59:265-304. [PubMed] [Google Scholar]

104. Mercer AJ, Stuart RC, Attard CA, Otero-Corchon V, Nillni EA, Low MJ. Temporal changes in nutritional state affect hypothalamic POMC peptide levels independently of leptin in adult male mice. Am J Physiol Endocrinol Metab. 2014;306:E904-E915. [PMC free article] [PubMed] [Google Scholar]

105. Barsh GS, Schwartz MW. Genetic approaches to studying energy balance: perception and integration. Nat Rev Genet. 2002;3:589-600. [PubMed] [Google Scholar]

106. Cowley MA, Smart JL, Rubinstein M, et al. Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature. 2001;411:480-484. [PubMed] [Google Scholar]

107. Williams KW, Margatho LO, Lee CE, et al. Segregation of acute leptin and insulin effects in distinct populations of arcuate proopiomelanocortin neurons. J Neurosci. 2010;30:2472-2479. [PMC free article] [PubMed] [Google Scholar]

108. Cowley MA, Pronchuk N, Fan W, Dinulescu DM, Colmers WF, Cone RD. Integration of NPY, AGRP, and melanocortin signals in the hypothalamic paraventricular nucleus: evidence of a cellular basis for the adipostat. Neuron. 1999;24:155-163. [PubMed] [Google Scholar]

109. Pinto S, Roseberry AG, Liu H, et al. Rapid rewiring of arcuate nucleus feeding circuits by leptin. Science. 2004;304:110-115. [PubMed] [Google Scholar]

110. Mizuno TM, Kleopoulos SP, Bergen HT, Roberts JL, Priest CA, Mobbs CV. Hypothalamic pro-opiomelanocortin mRNA is reduced by fasting and [corrected] in ob/ob and db/db mice, but is stimulated by leptin. Diabetes. 1998;47:294-297. [PubMed] [Google Scholar]

111. Schwartz MW, Seeley RJ, Woods SC, et al. Leptin increases hypothalamic pro-opiomelanocortin mRNA expression in the rostral arcuate nucleus. Diabetes. 1997;46:2119-2123. [PubMed] [Google Scholar]

112. Thornton JE, Cheung CC, Clifton DK, Steiner RA. Regulation of hypothalamic proopiomelanocortin mRNA by leptin in ob/ob mice. Endocrinology. 1997;138:5063-5066. [PubMed] [Google Scholar]

113. Benoit SC, Air EL, Coolen LM, et al. The catabolic action of insulin in the brain is mediated by melanocortins. J Neurosci. 2002;22:9048-9052. [PMC free article] [PubMed] [Google Scholar]

114. Seeley RJ, Yagaloff KA, Fisher SL, et al. Melanocortin receptors in leptin effects. Nature. 1997;390:349. [PubMed] [Google Scholar]

115. Halaas JL, Gajiwala KS, Maffei M, et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science. 1995;269:543-546. [PubMed] [Google Scholar]

116. Farooqi IS, Jebb SA, Langmack G, et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med. 1999;341:879-884. [PubMed] [Google Scholar]

117. Pelleymounter MA, Cullen MJ, Baker MB, et al. Effects of the obese gene product on body weight regulation in ob/ob mice. Science. 1995;269:540-543. [PubMed] [Google Scholar]

118. Ramachandrappa S, Farooqi IS. Genetic approaches to understanding human obesity. J Clin Invest. 2011;121:2080-2086. [PMC free article] [PubMed] [Google Scholar]

119. Halaas JL, Boozer C, Blair-West J, Fidahusein N, Denton DA, Friedman JM. Physiological response to long-term peripheral and central leptin infusion in lean and obese mice. Proc Natl Acad Sci U S A. 1997;94:8878-8883. [PMC free article] [PubMed] [Google Scholar]

120. Crujeiras AB, Goyenechea E, Abete I, et al. Weight regain after a diet-induced loss is predicted by higher baseline leptin and lower ghrelin plasma levels. J Clin Endocrinol Metab. 2010;95:5037-5044. [PubMed] [Google Scholar]

121. Knight ZA, Hannan KS, Greenberg ML, Friedman JM. Hyperleptinemia is required for the development of leptin resistance. PLoS One. 2010;5:e11376. [PMC free article] [PubMed] [Google Scholar]

122. Van Heek M, Compton DS, France CF, et al. Diet-induced obese mice develop peripheral, but not central, resistance to leptin. J Clin Invest. 1997;99:385-390. [PMC free article] [PubMed] [Google Scholar]

123. Banks WA, DiPalma CR, Farrell CL. Impaired transport of leptin across the blood-brain barrier in obesity. Peptides. 1999;20:1341-1345. [PubMed] [Google Scholar]

124. El-Haschimi K, Pierroz DD, Hileman SM, Bjørbaek C, Flier JS. Two defects contribute to hypothalamic leptin resistance in mice with diet-induced obesity. J Clin Invest. 2000;105:1827-1832. [PMC free article] [PubMed] [Google Scholar]

125. Björnholm M, Münzberg H, Leshan RL, et al. Mice lacking inhibitory leptin receptor signals are lean with normal endocrine function. J Clin Invest. 2007;117:1354-1360. [PMC free article] [PubMed] [Google Scholar]

126. Zabolotny JM, Bence-Hanulec KK, Stricker-Krongrad A, et al. PTP1B regulates leptin signal transduction in vivo. Dev Cell. 2002;2:489-495. [PubMed] [Google Scholar]

127. Hosoi T, Sasaki M, Miyahara T, Hashimoto C, Matsuo S, Yoshii M, Ozawa K. Endoplasmic reticulum stress induces leptin resistance. Mol Pharmacol. 2008;74:1610-1619. [PubMed] [Google Scholar]

128. Ozcan L, Ergin AS, Lu A, et al. Endoplasmic reticulum stress plays a central role in development of leptin resistance. Cell Metab. 2009;9:35-51. [PubMed] [Google Scholar]

129. Won JC, Jang PG, Namkoong C, et al. Central administration of an endoplasmic reticulum stress inducer inhibits the anorexigenic effects of leptin and insulin. Obesity (Silver Spring). 2009;17:1861-1865. [PubMed] [Google Scholar]

130. Wilsey J, Scarpace PJ. Caloric restriction reverses the deficits in leptin receptor protein and leptin signaling capacity associated with diet-induced obesity: role of leptin in the regulation of hypothalamic long-form leptin receptor expression. J Endocrinol. 2004;181:297-306. [PubMed] [Google Scholar]

131. Zhang Y, Scarpace PJ. The role of leptin in leptin resistance and obesity. Physiol Behav. 2006;88:249-256. [PubMed] [Google Scholar]

132. Starr R, Willson TA, Viney EM, et al. A family of cytokine-inducible inhibitors of signalling. Nature. 1997;387:917-921. [PubMed] [Google Scholar]

133. Bjorbaek C, Elmquist JK, Frantz JD, Shoelson SE, Flier JS. Identification of SOCS-3 as a potential mediator of central leptin resistance. Mol Cell. 1998;1:619-625. [PubMed] [Google Scholar]

134. Miller GD, Nicklas BJ, Fernandez A. Serial changes in inflammatory biomarkers after Roux-en-Y gastric bypass surgery. Surg Obes Relat Dis. 2011;7:618-624. [PMC free article] [PubMed] [Google Scholar]

135. Miller GD, Nicklas BJ, Davis CC, Ambrosius WT, Loeser RF, Messier SP. Is serum leptin related to physical function and is it modifiable through weight loss and exercise in older adults with knee osteoarthritis? Int J Obes Relat Metab Disord. 2004;28:1383-1390. [PubMed] [Google Scholar]

136. Hill JW, Elias CF, Fukuda M, et al. Direct insulin and leptin action on pro-opiomelanocortin neurons is required for normal glucose homeostasis and fertility. Cell Metab. 2010;11:286-297. [PMC free article] [PubMed] [Google Scholar]

137. Woods SC, Lotter EC, McKay LD, Porte D. Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons. Nature. 1979;282:503-505. [PubMed] [Google Scholar]

138. Spanswick D, Smith MA, Mirshamsi S, Routh VH, Ashford ML. Insulin activates ATP-sensitive K+ channels in hypothalamic neurons of lean, but not obese rats. Nat Neurosci. 2000;3:757-758. [PubMed] [Google Scholar]

139. Newgard CB, Lu D, Jensen MV, et al. Stimulus/secretion coupling factors in glucose-stimulated insulin secretion: insights gained from a multidisciplinary approach. Diabetes. 2002;51(suppl 3):S389-S393. [PubMed] [Google Scholar]

140. Polonsky KS, Given BD, Van Cauter E. Twenty-four-hour profiles and pulsatile patterns of insulin secretion in normal and obese subjects. J Clin Invest. 1988;81:442-448. [PMC free article] [PubMed] [Google Scholar]

141. Polonsky KS, Given BD, Hirsch L, et al. Quantitative study of insulin secretion and clearance in normal and obese subjects. J Clin Invest. 1988;81:435-441. [PMC free article] [PubMed] [Google Scholar]

142. Schwartz MW, Woods SC, Porte D, Jr, Seeley RJ, Baskin DG. Central nervous system control of food intake. Nature. 2000;661-671. [PubMed] [Google Scholar]

143. Air EL, Benoit SC, Blake Smith KA, Clegg DJ, Woods SC. Acute third ventricular administration of insulin decreases food intake in two paradigms. Pharmacol Biochem Behav. 2002;72:423-439. [PubMed] [Google Scholar]

144. Chavez M, Seeley RJ, Woods SC. A comparison between effects of intraventricular insulin and intraperitoneal lithium chloride on three measures sensitive to emetic agents. Behav Neurosci. 1995;109:547-550. [PubMed] [Google Scholar]

145. Baskin DG, Schwartz MW, Sipols AJ, D’Alessio DA, Goldstein BJ, White MF. Insulin receptor substrate-1 (IRS-1) expression in rat brain. Endocrinology. 1994;134:1952-1955. [PubMed] [Google Scholar]

146. Banks WA. The blood-brain barrier as a regulatory interface in the gut-brain axes. Physiol Behav. 2006;89:472-476. [PubMed] [Google Scholar]

147. Woods SC, Seeley RJ, Baskin DG, Schwartz MW. Insulin and the blood-brain barrier. Curr Pharm Des. 2003;9:795-800. [PubMed] [Google Scholar]

148. Air EL, Strowski MZ, Benoit SC, et al. Small molecule insulin mimetics reduce food intake and body weight and prevent development of obesity. Nat Med. 2002;8:179-183. [PubMed] [Google Scholar]

149. Brüning JC, Gautam D, Burks DJ, et al. Role of brain insulin receptor in control of body weight and reproduction. Science. 2000;289:2122-2125. [PubMed] [Google Scholar]

150. Wajchenberg BL. Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev. 2000;21:697-738. [PubMed] [Google Scholar]

151. Dua A, Hennes MI, Hoffmann RG, et al. Leptin: a significant indicator of total body fat but not of visceral fat and insulin insensitivity in African-American women. Diabetes. 1996;45:1635-1637. [PubMed] [Google Scholar]

152. Pouliot MC, Després JP, Nadeau A, et al. Visceral obesity in men. Associations with glucose tolerance, plasma insulin, and lipoprotein levels. Diabetes. 1992;41:826-834. [PubMed] [Google Scholar]

153. Bartness TJ, Shrestha YB, Vaughan CH, Schwartz GJ, Song CK. Sensory and sympathetic nervous system control of white adipose tissue lipolysis. Mol Cell Endocrinol. 2010;318:34-43. [PMC free article] [PubMed] [Google Scholar]

154. Shi H, Bartness TJ. White adipose tissue sensory nerve denervation mimics lipectomy-induced compensatory increases in adiposity. Am J Physiol Regul Integr Comp Physiol. 2005;289:R514-R520. [PubMed] [Google Scholar]

155. Morgan DA, Anderson EA, Mark AL. Renal sympathetic nerve activity is increased in obese Zucker rats. Hypertension. 1995;25:834-838. [PubMed] [Google Scholar]

156. Carlson SH, Shelton J, White CR, Wyss JM. Elevated sympathetic activity contributes to hypertension and salt sensitivity in diabetic obese Zucker rats. Hypertension. 2000;35:403-408. [PubMed] [Google Scholar]

157. Niijima A. Afferent signals from leptin sensors in the white adipose tissue of the epididymis, and their reflex effect in the rat. J Auton Nerv Syst. 1998;73:19-25. [PubMed] [Google Scholar]

158. Niijima A. Reflex effects from leptin sensors in the white adipose tissue of the epididymis to the efferent activity of the sympathetic and vagus nerve in the rat. Neurosci Lett. 1999;262:125-128. [PubMed] [Google Scholar]

159. Engelstoft MS, Egerod KL, Holst B, Schwartz TW. A gut feeling for obesity: 7TM sensors on enteroendocrine cells. Cell Metab. 2008;8:447-449. [PubMed] [Google Scholar]

160. Batterham RL, Bloom SR. The gut hormone peptide YY regulates appetite. Ann N Y Acad Sci. 2003;994:162-168. [PubMed] [Google Scholar]

161. Halatchev IG, Cone RD. Peripheral administration of PYY(3-36) produces conditioned taste aversion in mice. Cell Metab. 2005;1:159-168. [PubMed] [Google Scholar]

162. Richards P, Parker HE, Adriaenssens AE, et al. Identification and characterization of GLP-1 receptor-expressing cells using a new transgenic mouse model. Diabetes. 2014;63:1224-1233. [PMC free article] [PubMed] [Google Scholar]

163. Secher A, Jelsing J, Baquero AF, et al. The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss. J Clin Invest. 2014;124:4473-4488. [PMC free article] [PubMed] [Google Scholar]

164. Moran TH, Robinson PH, Goldrich MS, McHugh PR. Two brain cholecystokinin receptors: implications for behavioral actions. Brain Res. 1986;362:175-179. [PubMed] [Google Scholar]

165. Buchan AM, Polak JM, Solcia E, Capella C, Hudson D, Pearse AG. Electron immunohistochemical evidence for the human intestinal I cell as the source of CCK. Gut. 1978;19:403-407. [PMC free article] [PubMed] [Google Scholar]

166. Liddle RA, Goldfine ID, Rosen MS, Taplitz RA, Williams JA. Cholecystokinin bioactivity in human plasma. Molecular forms, responses to feeding, and relationship to gallbladder contraction. J Clin Invest. 1985;75:1144-1152. [PMC free article] [PubMed] [Google Scholar]

167. Rehfeld JF, Bungaard JR, Friis-Hansen L, Goetze JP. On the tissue-specific processing of procholecystokinin in the brain and gut: a short review. J Physiol Pharmacol. 2003;54(suppl 4):73-79. [PubMed] [Google Scholar]

168. Kissileff HR, Pi-Sunyer FX, Thornton J, Smith GP. C-terminal octapeptide of cholecystokinin decreases food intake in man. Am J Clin Nutr. 1981;34:154-160. [PubMed] [Google Scholar]

169. Ballinger A, McLoughlin L, Medbak S, Clark M. Cholecystokinin is a satiety hormone in humans at physiological post-prandial plasma concentrations. Clin Sci. 1995;89:375-381. [PubMed] [Google Scholar]

170. Schwartz GJ. The role of gastrointestinal vagal afferents in the control of food intake: current prospects. Nutrition. 2000;16:866-873. [PubMed] [Google Scholar]

171. Gibbs J, Young RC, Smith GP. Cholecystokinin decreases food intake in rats. J Comp Physiol Psychol. 1973;84:488-495. [PubMed] [Google Scholar]

172. Smith GP. Cholecystokinin and treatment of meal size: proof of principle. Obesity (Silver Spring). 2006;14(suppl 4):168S-170S. [PubMed] [Google Scholar]

173. Noble F, Wank SA, Crawley JN, et al. International Union of Pharmacology. XXI. Structure, distribution, and functions of cholecystokinin receptors. Pharmacol Rev. 1999;51:745-781. [PubMed] [Google Scholar]

174. French SJ, Murray B, Rumsey RD, Sepple CP, Read NW. Is cholecystokinin a satiety hormone? Correlations of plasma cholecystokinin with hunger, satiety and gastric emptying in normal volunteers. Appetite. 1993;21:95-104. [PubMed] [Google Scholar]

175. Berthoud HR. Interactions between the “cognitive” and “metabolic” brain in the control of food intake. Physiol Behav. 2007;91:486-498. [PubMed] [Google Scholar]

176. Moran TH. Gut peptides in the control of food intake: 30 years of ideas. Physiol Behav. 2004;82:175-180. [PubMed] [Google Scholar]

177. Strader AD, Woods SC. Gastrointestinal hormones and food intake. Gastroenterology. 2005;128:175-191. [PubMed] [Google Scholar]

178. West DB, Fey D, Woods SC. Cholecystokinin persistently suppresses meal size but not food intake in free-feeding rats. Am J Physiol. 1984;246:R776-R787. [PubMed] [Google Scholar]

179. Peters JH, Ritter RC, Simasko SM. Leptin and CCK selectively activate vagal afferent neurons innervating the stomach and duodenum. Am J Physiol Regul Integr Comp Physiol. 2006;290:R1544-R1549. [PubMed] [Google Scholar]

180. Nakazato M, Murakami N, Date Y, et al. A role for ghrelin in the central regulation of feeding. Nature. 2001;409:194-198. [PubMed] [Google Scholar]

181. Date Y, Shimbara T, Koda S, et al. Peripheral ghrelin transmits orexigenic signals through the noradrenergic pathway from the hindbrain to the hypothalamus. Cell Metab. 2006;4:323-331. [PubMed] [Google Scholar]

182. Date Y, Murakami N, Toshinai K, et al. The role of the gastric afferent vagal nerve in ghrelin-induced feeding and growth hormone secretion in rats. Gastroenterology. 2002;123:1120-1128. [PubMed] [Google Scholar]

183. Horvath TL, Diano S, Sotonyi P, Heiman M, Tschöp M. Minireview: ghrelin and the regulation of energy balance—a hypothalamic perspective. Endocrinology. 2001;142:4163-4169. [PubMed] [Google Scholar]

184. Zigman JM, Elmquist JK. Minireview: From anorexia to obesity: the yin and yang of body weight control. Endocrinology. 2003;144:3749-3756. [PubMed] [Google Scholar]

185. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999;402:656-660. [PubMed] [Google Scholar]

186. Asakawa A, Inui A, Kaga T, et al. Ghrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin. Gastroenterology. 2001;120:337-345. [PubMed] [Google Scholar]

187. Nakazato M, Murakami N, Date Y, et al. A role for ghrelin in the central regulation of feeding. Nature. 2001;409:194-198. [PubMed] [Google Scholar]

188. Shintani M, Ogawa Y, Ebihara K, et al. Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway. Diabetes. 2001;50:227-232. [PubMed] [Google Scholar]

189. Arvat E, Di Vito L, Broglio F, et al. Preliminary evidence that ghrelin, the natural GH secretagogue (GHS)-receptor ligand, strongly stimulates GH secretion in humans. J Endocrinol Invest. 2000;23:493-495. [PubMed] [Google Scholar]

190. Wu Q, Boyle MP, Palmiter RD. Loss of GABAergic signaling by AgRP neurons to the parabrachial nucleus leads to starvation. Cell. 2009;137:1225-1234. [PMC free article] [PubMed] [Google Scholar]

191. Wren AM, Seal LJ, Cohen MA, et al. Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab. 2001;86:5992. [PubMed] [Google Scholar]

192. Lawrence CB, Snape AC, Baudoin FMH, Luckman SM. Acute central ghrelin and GH secretagogues induce feeding and activate brain appetite centers. Endocrinology. 2002;143:155-162. [PubMed] [Google Scholar]

193. Wren AM, Small CJ, Ward HL, et al. The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology. 2000;141:4325-4328. [PubMed] [Google Scholar]

194. Tschöp M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents. Nature. 2000;407:908-913. [PubMed] [Google Scholar]

195. Zigman JM, Nakano Y, Coppari R, et al. Mice lacking ghrelin receptors resist the development of diet-induced obesity. J Clin Invest. 2005;115:3564-3572. [PMC free article] [PubMed] [Google Scholar]

196. Tong Q, Ye CP, Jones JE, Elmquist JK, Lowell BB. Synaptic release of GABA by AgRP neurons is required for normal regulation of energy balance. Nat Neurosci. 2008;11:998-1000. [PMC free article] [PubMed] [Google Scholar]

197. Kohno D, Yada T. Arcuate NPY neurons sense and integrate peripheral metabolic signals to control feeding. Neuropeptides. 2012;46:315-319. [PubMed] [Google Scholar]

198. Edholm T, Levin F, Hellström PM, Schmidt PT. Ghrelin stimulates motility in the small intestine of rats through intrinsic cholinergic neurons. Regul Pept. 2004;121:25-30. [PubMed] [Google Scholar]

199. Levin F, Edholm T, Ehrström M, et al. Effect of peripherally administered ghrelin on gastric emptying and acid secretion in the rat. Regul Pept. 2005;131:59-65. [PubMed] [Google Scholar]

200. Cummings DE, Purnell JQ, Frayo RS, Schmidova K, Wisse BE, Weigle DS. A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes. 2001;50:1714-1719. [PubMed] [Google Scholar]

201. Shiiya T, Nakazato M, Mizuta M, et al. Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J Clin Endocrinol Metab. 2002;87:240-244. [PubMed] [Google Scholar]

202. Ariyasu H, Takaya K, Tagami T, et al. Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans. J Clin Endocrinol Metab. 2001;86:4753-4758. [PubMed] [Google Scholar]

203. Cummings DE, Weigle DS, Frayo RS, et al. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med. 2002;346:1623-1630. [PubMed] [Google Scholar]

204. Michel MC, Beck-Sickinger A, Cox H, et al. XVI. International Union of Pharmacology recommendations for the nomenclature of neuropeptide Y, peptide YY, and pancreatic polypeptide receptors. Pharmacol Rev. 1998;50:143-150. [PubMed] [Google Scholar]

205. Baldock PA, Allison SJ, Lundberg P, et al. Novel role of Y1 receptors in the coordinated regulation of bone and energy homeostasis. J Biol Chem. 2007;282:19092-19102. [PubMed] [Google Scholar]

206. Sainsbury A, Schwarzer C, Couzens M, et al. Important role of hypothalamic Y2 receptors in body weight regulation revealed in conditional knockout mice. Proc Natl Acad Sci U S A. 2002;99:8938-8943. [PMC free article] [PubMed] [Google Scholar]

207. Batterham RL, Cowley MA, Small CJ, et al. Gut hormone PYY(3-36) physiologically inhibits food intake. Nature. 2002;418:650-654. [PubMed] [Google Scholar]

208. Al-Saffar A, Hellström PM, Nylander G. Correlation between peptide YY-induced myoelectric activity and transit of small-intestinal contents in rats. Scand J Gastroenterol. 1985;20:577-582. [PubMed] [Google Scholar]

209. Savage AP, Adrian TE, Carolan G, Chatterjee VK, Bloom SR. Effects of peptide YY (PYY) on mouth to caecum intestinal transit time and on the rate of gastric emptying in healthy volunteers. Gut. 1987;28:166-170. [PMC free article] [PubMed] [Google Scholar]

210. Symersky T, Biemond I, Frolich M, Masclee AAM. Effect of peptide YY on pancreatico-biliary secretion in humans. Scand J Gastroenterol. 2005;40:944-949. [PubMed] [Google Scholar]

211. Batterham RL, Cohen MA, Ellis SM, et al. Inhibition of food intake in obese subjects by peptide YY3-36. N Engl J Med. 2003;349:941-948. [PubMed] [Google Scholar]

212. Sam AH, Troke RC, Tan TM, Bewick GA. The role of the gut/brain axis in modulating food intake. Neuropharmacology. 2012;63:46-56. [PubMed] [Google Scholar]

213. Challis BG, Pinnock SB, Coll AP, Carter RN, Dickson SL, O’Rahilly S. Acute effects of PYY3-36 on food intake and hypothalamic neuropeptide expression in the mouse. Biochem Biophys Res Commun. 2003;311:915-919. [PubMed] [Google Scholar]

214. Chelikani PK, Haver AC, Reidelberger RD. Intravenous infusion of peptide YY(3-36) potently inhibits food intake in rats. Endocrinology. 2005;146:879-888. [PubMed] [Google Scholar]

215. Vrang N, Madsen AN, Tang-Christensen M, Hansen G, Larsen PJ. PYY(3-36) reduces food intake and body weight and improves insulin sensitivity in rodent models of diet-induced obesity. Am J Physiol Regul Integr Comp Physiol. 2006;291:R367-R375. [PubMed] [Google Scholar]

216. Vilsbøll T, Holst JJ. Incretins, insulin secretion and Type 2 diabetes mellitus. Diabetologia. 2004;47:357-366. [PubMed] [Google Scholar]

217. MacDonald PE, El-Kholy W, Riedel MJ, Salapatek AMF, Light PE, Wheeler MB. The multiple actions of GLP-1 on the process of glucose-stimulated insulin secretion. Diabetes. 2002;51(suppl 3):S434-S442. [PubMed] [Google Scholar]

218. Elliott RM, Morgan LM, Tredger JA, Deacon S, Wright J, Marks V. Glucagon-like peptide-1 (7-36)amide and glucose-dependent insulinotropic polypeptide secretion in response to nutrient ingestion in man: acute post-prandial and 24-h secretion patterns. J Endocrinol. 1993;138:159-166. [PubMed] [Google Scholar]

219. Nauck MA, Siemsglüss J, Orskov C, Holst JJ. Release of glucagon-like peptide 1 (GLP-1 [7-36 amide]), gastric inhibitory polypeptide (GIP) and insulin in response to oral glucose after upper and lower intestinal resections. Z Gastroenterol. 1996;34:159-166. [PubMed] [Google Scholar]

220. Pilichiewicz AN, Chaikomin R, Brennan IM, et al. Load-dependent effects of duodenal glucose on glycemia, gastrointestinal hormones, antropyloroduodenal motility, and energy intake in healthy men. Am J Physiol Endocrinol Metab. 2007;293:E743-E753. [PubMed] [Google Scholar]

221. Pilichiewicz AN, Papadopoulos P, Brennan IM, et al. Load-dependent effects of duodenal lipid on antropyloroduodenal motility, plasma CCK and PYY, and energy intake in healthy men. Am J Physiol Regul Integr Comp Physiol. 2007;293:R2170-R2178. [PubMed] [Google Scholar]

222. Todd JF, Edwards CM, Ghatei MA, Mather HM, Bloom SR. Subcutaneous glucagon-like peptide-1 improves postprandial glycaemic control over a 3-week period in patients with early type 2 diabetes. Clin Sci. 1998;95:325-329. [PubMed] [Google Scholar]

223. Orskov C. Glucagon-like peptide-1, a new hormone of the entero-insular axis. Diabetologia. 1992;35:701-711. [PubMed] [Google Scholar]

224. Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev. 2007;87:1409-1439. [PubMed] [Google Scholar]

225. Naslund E, Bogefors J, Skogar S, et al. GLP-1 slows solid gastric emptying and inhibits insulin, glucagon, and PYY release in humans. Am J Physiol. 1999;277:R910-R916. [PubMed] [Google Scholar]

226. Nauck MA, Niedereichholz U, Ettler R, et al. Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans. Am J Physiol. 1997;273:E981-E988. [PubMed] [Google Scholar]

227. Merchenthaler I, Lane M, Shughrue P. Distribution of pre-pro-glucagon and glucagon-like peptide-1 receptor messenger RNAs in the rat central nervous system. J Comp Neurol. 1999;403:261-280. [PubMed] [Google Scholar]

228. Jin SL, Han VK, Simmons JG, Towle AC, Lauder JM, Lund PK. Distribution of glucagonlike peptide I (GLP-I), glucagon, and glicentin in the rat brain: an immunocytochemical study. J Comp Neurol. 1988;271:519-532. [PubMed] [Google Scholar]

229. 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. [PMC free article] [PubMed] [Google Scholar]

230. Turton MD, O’Shea D, Gunn I, et al. A role for glucagon-like peptide-1 in the central regulation of feeding. Nature. 1996;379:69-72. [PubMed] [Google Scholar]

231. Scrocchi LA, Brown TJ, MaClusky N, et al. Glucose intolerance but normal satiety in mice with a null mutation in the glucagon-like peptide 1 receptor gene. Nat Med. 1996;2:1254-1258. [PubMed] [Google Scholar]

232. Hansotia T, Maida A, Flock G, et al. Extrapancreatic incretin receptors modulate glucose homeostasis, body weight, and energy expenditure. J Clin Invest. 2007;117:143-152. [PMC free article] [PubMed] [Google Scholar]

233. Tang-Christensen M, Vrang N, Larsen PJ. Glucagon-like peptide containing pathways in the regulation of feeding behaviour. Int J Obes Relat Metab Disord. 2001;25(suppl 5):S42-S47. [PubMed] [Google Scholar]

234. 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. 1998;274:R23-R29. [PubMed] [Google Scholar]

235. 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. [PMC free article] [PubMed] [Google Scholar]

236. Ranganath LR, Beety JM, Morgan LM, Wright JW, Howland R, Marks V. Attenuated GLP-1 secretion in obesity: cause or consequence? Gut. 1996;38:916-919. [PMC free article] [PubMed] [Google Scholar]

237. Meeran K, O’Shea D, Edwards CM, et al. Repeated intracerebroventricular administration of glucagon-like peptide-1-(7-36) amide or exendin-(9-39) alters body weight in the rat. Endocrinology. 1999;140:244-250. [PubMed] [Google Scholar]

238. Schjoldager B, Mortensen PE, Myhre J, Christiansen J, Holst JJ. Oxyntomodulin from distal gut. Role in regulation of gastric and pancreatic functions. Dig Dis Sci. 1989;34:1411-1419. [PubMed] [Google Scholar]

239. Wynne K, Park AJ, Small CJ, et al. Subcutaneous oxyntomodulin reduces body weight in overweight and obese subjects: a double-blind, randomized, controlled trial. Diabetes. 2005;54:2390-2395. [PubMed] [Google Scholar]

240. Wynne K, Park AJ, Small CJ, et al. Oxyntomodulin increases energy expenditure in addition to decreasing energy intake in overweight and obese humans: a randomised controlled trial. Int J Obes (Lond). 2006;30:1729-1736. [PubMed] [Google Scholar]

241. Dakin CL, Gunn I, Small CJ, et al. Oxyntomodulin inhibits food intake in the rat. Endocrinology. 2001;142:4244-4250. [PubMed] [Google Scholar]

242. Dakin CL, Small CJ, Batterham RL, et al. Peripheral oxyntomodulin reduces food intake and body weight gain in rats. Endocrinology. 2004;145:2687-2695. [PubMed] [Google Scholar]

243. Cowan E, Burch KJ, Green BD, Grieve DJ. Obestatin as a key regulator of metabolism and cardiovascular function with emerging therapeutic potential for diabetes. Br J Pharmacol. 2016;173:2165-2181. [PMC free article] [PubMed] [Google Scholar]

244. Shimizu H, Oh-I S, Hashimoto K, et al. Peripheral administration of nesfatin-1 reduces food intake in mice: the leptin-independent mechanism. Endocrinology. 2009;150:662-671. [PubMed] [Google Scholar]

245. Shimizu H, Ohsaki A, Oh-I S, Okada S, Mori M. A new anorexigenic protein, nesfatin-1. Peptides. 2009;30:995-998. [PubMed] [Google Scholar]

246. Iwasaki Y, Nakabayashi H, Kakei M, Shimizu H, Mori M, Yada T. Nesfatin-1 evokes Ca2+ signaling in isolated vagal afferent neurons via Ca2+ influx through N-type channels. Biochem Biophys Res Commun. 2009;390:958-962. [PubMed] [Google Scholar]

247. Crawley JN, Beinfeld MC. Rapid development of tolerance to the behavioural actions of cholecystokinin. Nature. 1983;302:703-706. [PubMed] [Google Scholar]

248. Heymsfield SB, Greenberg AS, Fujioka K, et al. Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA. 1999;282:1568-1575. [PubMed] [Google Scholar]

249. Erondu N, Wadden T, Gantz I, et al. Effect of NPY5R antagonist MK-0557 on weight regain after very-low-calorie diet-induced weight loss. Obesity (Silver Spring). 2007;15:895-905. [PubMed] [Google Scholar]

250. Tan T, Behary P, Tharakan G, et al. The effect of a subcutaneous infusion of GLP-1, OXM and PYY on energy intake and expenditure in obese volunteers [published online April 4, 2017]. J Clin Endocrinol Metab. doi: 10.1210/jc.2017-00469. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

251. Perry B, Wang Y. Appetite regulation and weight control: the role of gut hormones. Nutr Diabetes. 2012;2:e26. [PMC free article] [PubMed] [Google Scholar]

252. Williams KW, Elmquist JK. From neuroanatomy to behavior: central integration of peripheral signals regulating feeding behavior. Nat Neurosci. 2012;15:1350-1355. [PMC free article] [PubMed] [Google Scholar]

253. Vinik AI, Maser RE, Mitchell BD, Freeman R. Diabetic autonomic neuropathy. Diabetes Care. 2003;26:1553-1579. [PubMed] [Google Scholar]

254. Kentish S, Li H, Philp LK, et al. Diet-induced adaptation of vagal afferent function. J Physiol (Lond). 2012;590:209-221. [PMC free article] [PubMed] [Google Scholar]

255. Naznin F, Toshinai K, Waise TMZ, et al. Diet-induced obesity causes peripheral and central ghrelin resistance by promoting inflammation. J Endocrinol. 2015;226:81-92. [PMC free article] [PubMed] [Google Scholar]

256. Waise TMZ, Toshinai K, Naznin F, et al. One-day high-fat diet induces inflammation in the nodose ganglion and hypothalamus of mice. Biochem Biophys Res Commun. 2015;464:1157-1162. [PubMed] [Google Scholar]

257. Jordan SD, Könner AC, Brüning JC. Sensing the fuels: glucose and lipid signaling in the CNS controlling energy homeostasis. Cell Mol Life Sci. 2010;67:3255-3273. [PMC free article] [PubMed] [Google Scholar]

258. Belgardt BF, Brüning JC. CNS leptin and insulin action in the control of energy homeostasis. Ann N Y Acad Sci. 2010;1212:97-113. [PubMed] [Google Scholar]

259. Altman R, Rutledge JC. The vascular contribution to Alzheimer’s disease. Clin Sci. 2010;119:407-421. [PMC free article] [PubMed] [Google Scholar]

260. Anthony K, Reed LJ, Dunn JT, et al. Attenuation of insulin-evoked responses in brain networks controlling appetite and reward in insulin resistance: the cerebral basis for impaired control of food intake in metabolic syndrome? Diabetes. 2006;55:2986-2892. [PubMed] [Google Scholar]

261. Näslund E, Grybäck P, Backman L, et al. Distal small bowel hormones: correlation with fasting antroduodenal motility and gastric emptying. Dig Dis Sci. 1998;43:945-952. [PubMed] [Google Scholar]

262. Enriori PJ, Evans AE, Sinnayah P, et al. Diet-induced obesity causes severe but reversible leptin resistance in arcuate melanocortin neurons. Cell Metab. 2007;5:181-194. [PubMed] [Google Scholar]

263. Münzberg H, Flier JS, Bjørbaek C. Region-specific leptin resistance within the hypothalamus of diet-induced obese mice. Endocrinology. 2004;145:4880-4889. [PubMed] [Google Scholar]

264. Münzberg H, Björnholm M, Bates SH, Myers MG. Leptin receptor action and mechanisms of leptin resistance. Cell Mol Life Sci. 2005;62:642-652. [PubMed] [Google Scholar]

265. Lin S, Thomas TC, Storlien LH, Huang XF. Development of high fat diet-induced obesity and leptin resistance in C57Bl/6J mice. Int J Obes Relat Metab Disord. 2000;24:639-646. [PubMed] [Google Scholar]

266. Thaler JP, Yi CX, Schur EA, et al. Obesity is associated with hypothalamic injury in rodents and humans. J Clin Invest. 2012;122:153-162. [PMC free article] [PubMed] [Google Scholar]

267. Huang XF, Han M, Storlien LH. The level of NPY receptor mRNA expression in diet-induced obese and resistant mice. Brain Res Mol Brain Res. 2003;115:21-28. [PubMed] [Google Scholar]

268. Huang XF, Xin X, McLennan P, Storlien L. Role of fat amount and type in ameliorating diet-induced obesity: insights at the level of hypothalamic arcuate nucleus leptin receptor, neuropeptide Y and pro-opiomelanocortin mRNA expression. Diabetes Obes Metab. 2004;6:35-44. [PubMed] [Google Scholar]

269. Carvajal R, Wadden TA, Tsai AG, Peck K, Moran CH. Managing obesity in primary care practice: a narrative review. Ann N Y Acad Sci. 2013;1281:191-206. [PMC free article] [PubMed] [Google Scholar]

270. Bray GA, Frühbeck G, Ryan DH, Wilding JPH. Management of obesity. Lancet. 2016;387:1947-1956. [PubMed] [Google Scholar]

271. Farooqi IS, Wangensteen T, Collins S, et al. Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptor. N Engl J Med. 2007;356:237-247. [PMC free article] [PubMed] [Google Scholar]

272. Farooqi IS, O’Rahilly S. Monogenic obesity in humans. Annu Rev Med. 2005;56:443-458. [PubMed] [Google Scholar]

273. Santoro A, Mattace Raso G, Meli R. Drug targeting of leptin resistance. Life Sci. 2015;140:64-74. [PubMed] [Google Scholar]

274. Bhavsar S, Watkins J, Young A. Synergy between amylin and cholecystokinin for inhibition of food intake in mice. Physiol Behav. 1998;64:557-561. [PubMed] [Google Scholar]

275. Roth JD, Roland BL, Cole RL, 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. [PMC free article] [PubMed] [Google Scholar]

276. Trevaskis JL, Coffey T, Cole R, et al. Amylin-mediated restoration of leptin responsiveness in diet-induced obesity: magnitude and mechanisms. Endocrinology. 2008;149:5679-5687. [PubMed] [Google Scholar]

277. Williams DL, Baskin DG, Schwartz MW. Leptin regulation of the anorexic response to glucagon-like peptide-1 receptor stimulation. Diabetes. 2006;55:3387-3393. [PubMed] [Google Scholar]

278. Roujeau C, Jockers R, Dam J. New pharmacological perspectives for the leptin receptor in the treatment of obesity. Front Endocrinol (Lausanne). 2014;5:167. [PMC free article] [PubMed] [Google Scholar]

279. Kaszubska W, Falls HD, Schaefer VG, et al. Protein tyrosine phosphatase 1B negatively regulates leptin signaling in a hypothalamic cell line. Mol Cell Endocrinol. 2002;195:109-118. [PubMed] [Google Scholar]

280. Reed AS, Unger EK, Olofsson LE, Piper ML, Myers MG, Xu AW. Functional role of suppressor of cytokine signaling 3 upregulation in hypothalamic leptin resistance and long-term energy homeostasis. Diabetes. 2010;59:894-906. [PMC free article] [PubMed] [Google Scholar]

281. Ravussin E, Smith SR, Mitchell JA, et al. Enhanced weight loss with pramlintide/metreleptin: an integrated neurohormonal approach to obesity pharmacotherapy. Obesity (Silver Spring). 2009;17:1736-1743. [PMC free article] [PubMed] [Google Scholar]

282. Müller TD, Sullivan LM, Habegger K, 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. [PubMed] [Google Scholar]

283. Khera R, Murad MH, Chandar AK, et al. Association of pharmacological treatments for obesity with weight loss and adverse events: a systematic review and meta-analysis. JAMA. 2016;315:2424-2434. [PMC free article] [PubMed] [Google Scholar]

284. Smith SR, Weissman NJ, Anderson CM, et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med. 2010;363:245-256. [PubMed] [Google Scholar]

285. Yumuk V, Tsigos C, Fried M, et al. European guidelines for obesity management in adults. Obes Facts. 2015;8:402-424. [PMC free article] [PubMed] [Google Scholar]

287. Troke RC, Tan TM, Bloom SR. The future role of gut hormones in the treatment of obesity. Ther Adv Chronic Dis. 2014;5:4-14. [PMC free article] [PubMed] [Google Scholar]

288. Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375:1834-1844. [PubMed] [Google Scholar]

289. Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:311-322. [PMC free article] [PubMed] [Google Scholar]

290. Colbert JA, Jangi S. Training physicians to manage obesity: back to the drawing board. N Engl J Med. 2013;369:1389-1391. [PubMed] [Google Scholar]

291. Lawson EA, Marengi DA, DeSanti RL, Holmes TM, Schoenfeld DA, Tolley CJ. Oxytocin reduces caloric intake in men. Obesity (Silver Spring). 2015;23:950-956. [PMC free article] [PubMed] [Google Scholar]

292. Iwasaki Y, Maejima Y, Suyama S, et al. Peripheral oxytocin activates vagal afferent neurons to suppress feeding in normal and leptin-resistant mice: a route for ameliorating hyperphagia and obesity. Am J Physiol Regul Integr Comp Physiol. 2015;308:R360-R369. [PubMed] [Google Scholar]

293. Borowsky B, Durkin MM, Ogozalek K, et al. Antidepressant, anxiolytic and anorectic effects of a melanin-concentrating hormone-1 receptor antagonist. Nat Med. 2002;8:825-830. [PubMed] [Google Scholar]

294. Ito M, Ishihara A, Gomori A, et al. Melanin-concentrating hormone 1-receptor antagonist suppresses body weight gain correlated with high receptor occupancy levels in diet-induced obesity mice. Eur J Pharmacol. 2009;624:77-83. [PubMed] [Google Scholar]

295. Li Z, Maglione M, Tu W, et al. Meta-analysis: pharmacologic treatment of obesity. Ann Intern Med. 2005;142:532-546. [PubMed] [Google Scholar]

296. Maayan L, Vakhrusheva J, Correll CU. Effectiveness of medications used to attenuate antipsychotic-related weight gain and metabolic abnormalities: a systematic review and meta-analysis. Neuropsychopharmacology. 2010;35:1520-1530. [PMC free article] [PubMed] [Google Scholar]

297. Gadde KM, Franciscy DM, Wagner HR, Krishnan KRR. Zonisamide for weight loss in obese adults: a randomized controlled trial. JAMA. 2003;289:1820-1825. [PubMed] [Google Scholar]

298. Singh-Franco D, Perez A, Harrington C. The effect of pramlintide acetate on glycemic control and weight in patients with type 2 diabetes mellitus and in obese patients without diabetes: a systematic review and meta-analysis. Diabetes Obes Metab. 2011;13:169-180. [PubMed] [Google Scholar]

299. Chen KY, Muniyappa R, Abel BS, et al. RM-493, a melanocortin-4 receptor (MC4R) agonist, increases resting energy expenditure in obese individuals. J Clin Endocrinol Metab. 2015;100:1639-1645. [PMC free article] [PubMed] [Google Scholar]

300. Martinussen C, Bojsen-Moller KN, Svane MS, Dejgaard TF, Madsbad S. Emerging drugs for the treatment of obesity. Expert Opin Emerg Drugs. 2017;22:87-99. [PubMed] [Google Scholar]

301. Balthasar N, Dalgaard LT, Lee CE, et al. Divergence of melanocortin pathways in the control of food intake and energy expenditure. Cell. 2005;123:493-505. [PubMed] [Google Scholar]

302. Astrup A, Madsbad S, Breum L, Jensen TJ, Kroustrup JP, Larsen TM. Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372:1906-1913. [PubMed] [Google Scholar]

303. Gilbert JA, Gasteyger C, Raben A, Meier DH, Astrup A, Sjödin A. The effect of tesofensine on appetite sensations. Obesity (Silver Spring). 2012;20:553-561. [PubMed] [Google Scholar]

304. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117-2128. [PubMed] [Google Scholar]

305. Joharapurkar AA, Dhanesha NA, Jain MR. Inhibition of the methionine aminopeptidase 2 enzyme for the treatment of obesity. Diabetes Metab Syndr Obes. 2014;7:73-84. [PMC free article] [PubMed] [Google Scholar]

306. Yu XX, Watts LM, Manchem VP, et al. Peripheral reduction of FGFR4 with antisense oligonucleotides increases metabolic rate and lowers adiposity in diet-induced obese mice. PLoS One. 2013;8:e66923. [PMC free article] [PubMed] [Google Scholar]

307. Timmers S, Konings E, Bilet L, et al. Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab. 2011;14:612-622. [PMC free article] [PubMed] [Google Scholar]

308. Omori N, Kouyama N, Yukimasa A, et al. Hit to lead SAR study on benzoxazole derivatives for an NPY Y5 antagonist. Bioorg Med Chem Lett. 2012;22:2020-2023. [PubMed] [Google Scholar]

309. Tschöp MH, Finan B, Clemmensen C, et al. Unimolecular polypharmacy for treatment of diabetes and obesity. Cell Metab. 2016;24:51-62. [PubMed] [Google Scholar]

What is a chemical messengers secreted by fat cells that act as an appetite suppressant?

The hormone leptin is produced by fat cells and is secreted into our bloodstream. Leptin reduces a person's appetite by acting on specific centres of their brain to reduce their urge to eat. It also seems to control how the body manages its store of body fat.

Which of the following describes the Yerkes Dodson law?

According to what is known as “The Yerkes-Dodson law,” performance increases with physiological or mental arousal (stress) but only up to a point. When the level of stress becomes too high, performance decreases.

Which of the following model of motivation is compared to how a thermostat operates?

Homeostatic motivation has often been compared with the operation of a thermostat that regulates a room's tem- perature.

Who proposed the hierarchy of needs quizlet?

Maslow's hierarchy of needs is a theory in psychology introduced by Abraham Maslow in his 1943 paper; A Theory of Human Motivation; this theory was fully expressed in his book, Motivation and Personality.