Translational and therapeutic potential of oxytocin as an anti-obesity strategy: Insights from rodents, nonhuman primates and humans

Physiology and Behavior

Volumn 152, Issue , 2015, Pages 438-449

  Blevins, James E ^a,b   Baskin, Denis G ^a,b  

^a VA PUGET SOUND HEALTH CARE SYSTEM   (United States)

^b UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

Author keywords

Energy expenditure; Food intake; Obesity; Oxytocin

Indexed keywords

CHOLESTEROL; LEPTIN; OXYTOCIN; ANTIOBESITY AGENT;

ANIMAL MODEL; ARTICLE; BODY WEIGHT; CENTRAL NERVOUS SYSTEM; DRUG DISTRIBUTION; ENERGY BALANCE; ENERGY EXPENDITURE; FAT MASS; GASTROINTESTINAL TRACT; HUMAN; HYPERLIPIDEMIA; LIPID DIET; LIPOLYSIS; NODOSE GANGLION; NONHUMAN; OBESITY; PRIMATE; PRIORITY JOURNAL; RODENT; SEX DIFFERENCE; SIGNAL TRANSDUCTION; WEIGHT GAIN; ANIMAL; PATHOPHYSIOLOGY; PROCEDURES; TRANSLATIONAL RESEARCH;

ANIMALS; ANTI-OBESITY AGENTS; HUMANS; OBESITY; OXYTOCIN; PRIMATES; RODENTIA; TRANSLATIONAL MEDICAL RESEARCH;

EID: 84961136644     PISSN: 00319384     EISSN: 1873507X     Source Type: Journal    
DOI: 10.1016/j.physbeh.2015.05.023     Document Type: Article

References (241)

1. Cornier M.A., Dabelea D., Hernandez T.L., Lindstrom R.C., Steig A.J., Stob N.R., et al. The metabolic syndrome. Endocr. Rev. 2008, 29:777-822.
2. Eckel R.H., Grundy S.M., Zimmet P.Z. The metabolic syndrome. Lancet 2005, 365:1415-1428.
3. Grundy S.M. Metabolic syndrome pandemic. Arterioscler. Thromb. Vasc. Biol. 2008, 28:629-636.
4. Smyth S., Heron A. Diabetes and obesity: the twin epidemics. Nat. Med. 2006, 12:75-80.
5. Finkelstein E.A., Trogdon J.G., Cohen J.W., Dietz W. Annual medical spending attributable to obesity: payer-and service-specific estimates. Health Aff. 2009, 28:w822-w831.
6. Ogden C.L., Carroll M.D., Kit B.K., Flegal K.M. Prevalence of obesity in the United States, 2009-2010. NCHS Data Brief 2012.
7. Bray G.A., Nielsen S.J., Popkin B.M. Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity. The American Journal of Clinical Nutrition 2004, 79:537-543.
8. Havel P.J. Dietary fructose: implications for dysregulation of energy homeostasis and lipid/carbohydrate metabolism. Nutr. Rev. 2005, 63:133-157.
9. Malik V.S., Popkin B.M., Bray G.A., Despres J.P., Hu F.B. Sugar-sweetened beverages, obesity, type 2 diabetes mellitus, and cardiovascular disease risk. Circulation 2010, 121:1356-1364.
10. Malik V.S., Schulze M.B., Hu F.B. Intake of sugar-sweetened beverages and weight gain: a systematic review. The American Journal of Clinical Nutrition 2006, 84:274-288.
11. Stanhope K.L., Havel P.J. Fructose consumption: potential mechanisms for its effects to increase visceral adiposity and induce dyslipidemia and insulin resistance. Curr. Opin. Lipidol. 2008, 19:16-24.
12. Stanhope K.L., Schwarz J.M., Keim N.L., Griffen S.C., Bremer A.A., Graham J.L., et al. Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans. J. Clin. Invest. 2009, 119:1322-1334.
13. Bremer A.A., Stanhope K.L., Graham J.L., Cummings B.P., Wang W., Saville B.R., et al. Fructose-fed rhesus monkeys: a nonhuman primate model of insulin resistance, metabolic syndrome, and type 2 diabetes. Clinical and Translational Science 2011, 4:243-252.
14. Page K.A., Chan O., Arora J., Belfort-Deaguiar R., Dzuira J., Roehmholdt B., et al. Effects of fructose vs glucose on regional cerebral blood flow in brain regions involved with appetite and reward pathways. JAMA: The Journal of the American Medical Association 2013, 309:63-70.
15. Covasa M., Grahn J., Ritter R.C. High fat maintenance diet attenuates hindbrain neuronal response to CCK. Regul. Pept. 2000, 86:83-88.
16. Covasa M., Ritter R.C. Rats maintained on high-fat diets exhibit reduced satiety in response to CCK and bombesin. Peptides 1998, 19:1407-1415.
17. Covasa M., Ritter R.C. Reduced sensitivity to the satiation effect of intestinal oleate in rats adapted to high-fat diet. Am. J. Phys. 1999, 277:R279-R285.
18. Braude R., Mitchell K.G. Observations on the relationship between oxytocin and adrenaline in milk ejection in the sow. The Journal of Endocrinology 1952, 8:238-241.
19. den Hertog C.E., de Groot A.N., van Dongen P.W. History and use of oxytocics. Eur. J. Obstet. Gynecol. Reprod. Biol. 2001, 94:8-12.
20. Verbalis J.G., Blackburn R.E., Hoffman G.E., Stricker E.M. Establishing behavioral and physiological functions of central oxytocin: insights from studies of oxytocin and ingestive behaviors. Adv. Exp. Med. Biol. 1995, 395:209-225.
21. Striepens N., Kendrick K.M., Maier W., Hurlemann R. Prosocial effects of oxytocin and clinical evidence for its therapeutic potential. Front. Neuroendocrinol. 2011, 32:426-450.
22. Yamasue H., Yee J.R., Hurlemann R., Rilling J.K., Chen F.S., Meyer-Lindenberg A., et al. Integrative approaches utilizing oxytocin to enhance prosocial behavior: from animal and human social behavior to autistic social dysfunction. J Neurosci. 2012, 32:14109-14117.
23. Montag C., Brockmann E.M., Bayerl M., Rujescu D., Muller D.J., Gallinat J. Oxytocin and oxytocin receptor gene polymorphisms and risk for schizophrenia: a case-control study. The world journal of biological psychiatry: the official journal of the World Federation of Societies of Biological Psychiatry 2012.
24. Miller G. Neuroscience. The promise and perils of oxytocin. Science 2013, 339:267-269.
25. Young L.J., Barrett C.E. Neuroscience. Can oxytocin treat autism?. Science 2015, 347:825-826.
26. Blevins J.E., Graham J.L., Morton G.J., Bales K.L., Schwartz M.W., Baskin D.G., et al. Chronic oxytocin administration inhibits food intake, increases energy expenditure, and produces weight loss in fructose-fed obese rhesus monkeys. Am J Physiol-Reg I 2014.
27. Deblon N., Veyrat-Durebex C., Bourgoin L., Caillon A., Bussier A.L., Petrosino S., et al. Mechanisms of the anti-obesity effects of oxytocin in diet-induced obese rats. PLoS One 2011, 6. e25565.
28. 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 2011, 3:1169-1177.
29. Maejima Y., Sedbazar U., Suyama S., Kohno D., Onaka T., Takano E., 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.
30. Morton G.J., Thatcher B.S., Reidelberger R.D., Ogimoto K., Wolden-Hanson T., Baskin D.G., et al. Peripheral oxytocin suppresses food intake and causes weight loss in diet-induced obese rats. Am J Physiol-Endoc M. 2012, 302:E134-E144.
31. Zhang G., Bai H., Zhang H., Dean C., Wu Q., Li J., et al. Neuropeptide exocytosis involving synaptotagmin-4 and oxytocin in hypothalamic programming of body weight and energy balance. Neuron 2011, 69:523-535.
32. 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.
33. Zhang H., Wu C., Chen Q., Chen X., Xu Z., Wu J., et al. Treatment of obesity and diabetes using oxytocin or analogs in patients and mouse models. PLoS One 2013, 8. e61477.
34. Lawson E.A., Marengi D.A., DeSanti R.L., Holmes T.M., Schoenfeld D.A., Tolley C.J. Oxytocin reduces caloric intake in men. Obesity 2015.
35. Ott V., Finlayson G., Lehnert H., Heitmann B., Heinrichs M., Born J., et al. Oxytocin reduces reward-driven food intake in humans. Diabetes 2013, 62:3418-3425.
36. Kublaoui B.M., Gemelli T., Tolson K.P., Wang Y., Zinn A.R. Oxytocin deficiency mediates hyperphagic obesity of Sim1 haploinsufficient mice. Mol. Endocrinol. 2008, 22:1723-1734.
37. Tung Y.C., Ma M., Piper S., Coll A., O'Rahilly S., Yeo G.S. Novel leptin-regulated genes revealed by transcriptional profiling of the hypothalamic paraventricular nucleus. J Neurosci. 2008, 28:12419-12426.
38. 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.
39. Sawchenko P.E., Swanson L.W. 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.
40. Swaab D.F., Nijveldt F., Pool C.W. Distribution of oxytocin and vasopressin in the rat supraoptic and paraventricular nucleus. The Journal of Endocrinology 1975, 67:461-462.
41. Swaab D.F., Pool C.W., Nijveldt F. Immunofluorescence of vasopressin and oxytocin in the rat hypothalamo-neurohypophypopseal system. J. Neural Transm. 1975, 36:195-215.
42. Sawchenko P.E., Swanson L.W., Vale W.W. Corticotropin-releasing factor: co-expression within distinct subsets of oxytocin-, vasopressin-, and neurotensin-immunoreactive neurons in the hypothalamus of the male rat. J Neurosci. 1984, 4:1118-1129.
43. Kawata M., Sano Y. Immunohistochemical identification of the oxytocin and vasopressin neurons in the hypothalamus of the monkey (Macaca fuscata). Anat. Embryol. 1982, 165:151-167.
44. Antunes J.L., Zimmerman E.A. The hypothalamic magnocellular system of the rhesus monkey: an immunocytochemical study. J. Comp. Neurol. 1978, 181:539-565.
45. Ginsberg S.D., Hof P.R., Young W.G., Morrison J.H. Noradrenergic innervation of vasopressin- and oxytocin-containing neurons in the hypothalamic paraventricular nucleus of the macaque monkey: quantitative analysis using double-label immunohistochemistry and confocal laser microscopy. J. Comp. Neurol. 1994, 341:476-491.
46. Sofroniew M.V., Weindl A., Schrell U., Wetzstein R. Immunohistochemistry of vasopressin, oxytocin and neurophysin in the hypothalamus and extrahypothalamic regions of the human and primate brain. Acta Histochem. Suppl. 1981, 24:79-95.
47. Sukhov R.R., Walker L.C., Rance N.E., Price D.L., Young W.S. Vasopressin and oxytocin gene expression in the human hypothalamus. J. Comp. Neurol. 1993, 337:295-306.
48. Dierickx K., Vandesande F. Immunocytochemical localization of the vasopressinergic and the oxytocinergic neurons in the human hypothalamus. Cell Tissue Res. 1977, 184:15-27.
49. Paulin C., Dubois P.M., Czernichow P., Dubois M.P. Immunocytological evidence for oxytocin neurons in the human fetal hypothalamus. Cell Tissue Res. 1978, 188:259-264.
50. George J.M. Immunoreactive vasopressin and oxytocin: concentration in individual human hypothalamic nuclei. Science 1978, 200:342-343.
51. Koutcherov Y., Mai J.K., Ashwell K.W., Paxinos G. Organization of the human paraventricular hypothalamic nucleus. J. Comp. Neurol. 2000, 423:299-318.
52. Gimpl G., Fahrenholz F. The oxytocin receptor system: structure, function, and regulation. Physiol. Rev. 2001, 81:629-683.
53. Ragen B.J., Bales K.L. Oxytocin and vasopressin in non-human primates. Oxytocin, Vasopressin and Related Peptides in the Regulation of Behavior 2013, 288-306. Cambridge University Press, Cambridge, United Kingdom. E. Choleris, D.W. Pfaff, M. Kavaliers (Eds.).
54. Rosen G.J., de Vries G.J., Goldman S.L., Goldman B.D., Forger N.G. Distribution of oxytocin in the brain of a eusocial rodent. Neuroscience 2008, 155:809-817.
55. Vaughan C.H., Shrestha Y.B., Bartness T.J. Characterization of a novel melanocortin receptor-containing node in the SNS outflow circuitry to brown adipose tissue involved in thermogenesis. Brain Res. 2011, 1411:17-27.
56. Maejima Y., Sakuma K., Santoso P., Gantulga D., Katsurada K., Ueta Y., et al. Oxytocinergic circuit from paraventricular and supraoptic nuclei to arcuate POMC neurons in hypothalamus. FEBS Lett. 2014, 588:4404-4412.
57. Shahrokh D.K., Zhang T.Y., Diorio J., Gratton A., Meaney M.J. Oxytocin-dopamine interactions mediate variations in maternal behavior in the rat. Endocrinology 2010, 151:2276-2286.
58. Jankowski M., Hajjar F., Kawas S.A., Mukaddam-Daher S., Hoffman G., McCann S.M., et al. Rat heart: a site of oxytocin production and action. Proc. Natl. Acad. Sci. U. S. A. 1998, 95:14558-14563.
59. Ohlsson B., Truedsson M., Djerf P., Sundler F. Oxytocin is expressed throughout the human gastrointestinal tract. Regul. Pept. 2006, 135:7-11.
60. Welch M.G., Tamir H., Gross K.J., Chen J., Anwar M., Gershon M.D. Expression and developmental regulation of oxytocin (OT) and oxytocin receptors (OTR) in the enteric nervous system (ENS) and intestinal epithelium. J. Comp. Neurol. 2009, 512:256-270.
61. Qin J., Feng M., Wang C., Ye Y., Wang P.S., Liu C. Oxytocin receptor expressed on the smooth muscle mediates the excitatory effect of oxytocin on gastric motility in rats. Neurogastroenterology and motility: the official journal of the European Gastrointestinal Motility Society. 2009, 21:430-438.
62. Altirriba J., Poher A.L., Caillon A., Arsenijevic D., Veyrat-Durebex C., Lyautey J., et al. Divergent effects of oxytocin treatment of obese diabetic mice on adiposity and diabetes. Endocrinology 2014, en20141466.
63. Gajdosechova L., Krskova K., Olszanecki R., Zorad S. Differential regulation of oxytocin receptor in various adipose tissue depots and skeletal muscle types in obese Zucker rats. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 2015.
64. Gajdosechova L., Krskova K., Segarra A.B., Spolcova A., Suski M., Olszanecki R., et al. Hypooxytocinaemia in obese Zucker rats relates to oxytocin degradation in liver and adipose tissue. The Journal of Endocrinology 2014, 220:333-343.
65. Muchmore D.B., Little S.A., de Haen C. A dual mechanism of action of ocytocin in rat epididymal fat cells. The Journal of Biological Chemistry 1981, 256:365-372.
66. Schaffler A., Binart N., Scholmerich J., Buchler C. Hypothesis paper: brain talks with fat-evidence for a hypothalamic-pituitary-adipose axis?. Neuropeptides 2005, 39:363-367.
67. Tsuda T., Ueno Y., Yoshikawa T., Kojo H., Osawa T. Microarray profiling of gene expression in human adipocytes in response to anthocyanins. Biochem. Pharmacol. 2006, 71:1184-1197.
68. Yi K., So K., Hata Y., Suzuki Y., Kato D., Watanabe K., et al. The regulation of oxytocin receptor gene expression during adipogenesis. J. Neuroendocrinol. 2015.
69. Gould B.R., Zingg H.H. Mapping oxytocin receptor gene expression in the mouse brain and mammary gland using an oxytocin receptor-LacZ reporter mouse. Neuroscience 2003, 122:155-167.
70. Verbalis J.G. The brain oxytocin receptor(s)?. Front. Neuroendocrinol. 1999, 20:146-156.
71. Yoshida M., Takayanagi Y., Inoue K., Kimura T., Young L.J., Onaka T., et al. Evidence that oxytocin exerts anxiolytic effects via oxytocin receptor expressed in serotonergic neurons in mice. J Neurosci. 2009, 29:2259-2271.
72. Tribollet E., Dubois-Dauphin M., Dreifuss J.J., Barberis C., Jard S. Oxytocin receptors in the central nervous system. Distribution, development, and species differences. Ann. N. Y. Acad. Sci. 1992, 652:29-38.
73. Boccia M.L., Panicker A.K., Pedersen C., Petrusz P. Oxytocin receptors in non-human primate brain visualized with monoclonal antibody. Neuroreport 2001, 12:1723-1726.
74. Freeman S.M., Inoue K., Smith A.L., Goodman M.M., Young L.J. The neuroanatomical distribution of oxytocin receptor binding and mRNA in the male rhesus macaque (Macaca mulatta). Psychoneuroendocrinology 2014, 45:128-141.
75. Schorscher-Petcu A., Dupre A., Tribollet E. Distribution of vasopressin and oxytocin binding sites in the brain and upper spinal cord of the common marmoset. Neurosci. Lett. 2009, 461:217-222.
76. Boccia M.L., Petrusz P., Suzuki K., Marson L., Pedersen C.A. Immunohistochemical localization of oxytocin receptors in human brain. Neuroscience 2013, 253:155-164.
77. Loup F., Tribollet E., Dubois-Dauphin M., Pizzolato G., Dreifuss J.J. Localization of oxytocin binding sites in the human brainstem and upper spinal cord: an autoradiographic study. Brain Res. 1989, 500:223-230.
78. Loup F., Tribollet E., Dubois-Dauphin M., Dreifuss J.J. Localization of high-affinity binding sites for oxytocin and vasopressin in the human brain. An autoradiographic study. Brain Res. 1991, 555:220-232.
79. Arletti R., Benelli A., Bertolini A. Influence of oxytocin on feeding behavior in the rat. Peptides 1989, 10:89-93.
80. Arletti R., Benelli A., Bertolini A. Oxytocin inhibits food and fluid intake in rats. Physiol. Behav. 1990, 48:825-830.
81. Blevins J.E., Eakin T.J., Murphy J.A., Schwartz M.W., Baskin D.G. Oxytocin innervation of caudal brainstem nuclei activated by cholecystokinin. Brain Res. 2003, 993:30-41.
82. Blevins J.E., Schwartz M.W., Baskin D.G. Evidence that paraventricular nucleus oxytocin neurons link hypothalamic leptin action to caudal brain stem nuclei controlling meal size. Am J Physiol Regul Integr Comp Physiol. 2004, 287:R87-R96.
83. Maejima Y., Rita R.S., Santoso P., Aoyama M., Hiraoka Y., Nishimori K., et al. Nasal oxytocin administration reduces food intake without affecting locomotor activity and glycemia with c-Fos induction in limited brain areas. Neuroendocrinology 2015.
84. Olson B.R., Drutarosky M.D., Chow M.S., Hruby V.J., Stricker E.M., Verbalis J.G. Oxytocin and an oxytocin agonist administered centrally decrease food intake in rats. Peptides 1991, 1991:113-118.
85. Olson B.R., Drutarosky M.D., Stricker E.M., Verbalis J.G. Brain oxytocin receptor antagonism blunts the effects of anorexigenic treatments in rats: evidence for central oxytocin inhibition of food intake. Endocrinology 1991, 129:785-791.
86. Lokrantz C.M., Uvnas-Moberg K., Kaplan J.M. Effects of central oxytocin administration on intraoral intake of glucose in deprived and nondeprived rats. Physiol. Behav. 1997, 62:347-352.
87. Wu Z., Xu Y., Zhu Y., Sutton A.K., Zhao R., Lowell B.B., et al. An obligate role of oxytocin neurons in diet induced energy expenditure. PLoS One 2012, 7:e45167.
88. Ong Z.Y., Alhadeff A.L., Grill H.J. Medial nucleus tractus solitarius oxytocin receptor signaling and food intake control: the role of gastrointestinal satiation signal processing. Am J Physiol Regul Integr Comp Physiol. 2015, 10.1152/ajpregu.00534.2014.
89. Sutton A.K., Pei H., Burnett K.H., Myers M.G., Rhodes C.J., Olson D.P. Control of food intake and energy expenditure by Nos1 neurons of the paraventricular hypothalamus. J Neurosci. 2014, 34:15306-15318.
90. Camerino C. Low sympathetic tone and obese phenotype in oxytocin-deficient mice. Obesity 2009, 17:980-984.
91. 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.
92. Wheeler E., Huang N., Bochukova E.G., Keogh J.M., Lindsay S., Garg S., et al. Genome-wide SNP and CNV analysis identifies common and low-frequency variants associated with severe early-onset obesity. Nat. Genet. 2013.
93. Plante E., Menaouar A., Danalache B.A., Yip D., Broderick T.L., Chiasson J., et al. Oxytocin treatment prevents the cardiomyopathy observed in obese diabetic Male db/db mice. Endocrinology 2015, 10.1210/en.2014-1718.
94. Qian W., Zhu T., Tang B., Yu S., Hu H., Sun W., et al. Decreased circulating levels of oxytocin in obesity and newly diagnosed type 2 diabetic patients. J. Clin. Endocrinol. Metab. 2014, 99:4683-4689.
95. Northway M.G., Morris M., Geisinger K.R., MacLean D.B. Effects of a gastric implant on body weight and gastrointestinal hormones in cafeteria diet obese rats. Physiol. Behav. 1989, 45:331-335.
96. Schroeder M., Gelber V., Moran T.H., Weller A. Long-term obesity levels in female OLETF rats following time-specific post-weaning food restriction. Horm. Behav. 2010, 58:844-853.
97. Schroeder M., Moran T.H., Weller A. Attenuation of obesity by early-life food restriction in genetically hyperphagic male OLETF rats: peripheral mechanisms. Horm. Behav. 2010, 57:455-462.
98. Schroeder M., Zagoory-Sharon O., Shbiro L., Marco A., Hyun J., Moran T.H., et al. Development of obesity in the Otsuka Long-Evans Tokushima Fatty rat. Am J Physiol Regul Integr Comp Physiol. 2009, 297:R1749-R1760.
99. Stock S., Granstrom L., Backman L., Matthiesen A.S., Uvnas-Moberg K. Elevated plasma levels of oxytocin in obese subjects before and after gastric banding. Int. J. Obes. 1989, 13:213-222.
100. Lawson E.A., Donoho D.A., Blum J.I., Meenaghan E.M., Misra M., Herzog D.B., et al. Decreased nocturnal oxytocin levels in anorexia nervosa are associated with low bone mineral density and fat mass. The Journal of Clinical Psychiatry 2011, 72:1546-1551.
101. Lawson E.A., Ackerman K.E., Estella N.M., Guereca G., Pierce L., Sluss P.M., et al. Nocturnal oxytocin secretion is lower in amenorrheic athletes than nonathletes and associated with bone microarchitecture and finite element analysis parameters. European journal of endocrinology/European Federation of Endocrine Societies 2013, 168:457-464.
102. Lawson E.A., Ackerman K.E., Slattery M., Marengi D.A., Clarke H., Misra M. Oxytocin secretion is related to measures of energy homeostasis in young amenorrheic athletes. J. Clin. Endocrinol. Metab. 2014, 99:E881-E885.
103. Butler M.G. Prader-Willi syndrome: obesity due to genomic imprinting. Current Genomics 2011, 12:204-215.
104. Swaab D.F., Purba J.S., Hofman M.A. Alterations in the hypothalamic paraventricular nucleus and its oxytocin neurons (putative satiety cells) in Prader-Willi syndrome: a study of five cases. J. Clin. Endocrinol. Metab. 1995, 80:573-579.
105. Iwasaki Y., Maejima Y., Suyama S., Yoshida M., Arai T., Katsurada K., 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. 2014, 10.1152/ajpregu.00344.2014.
106. Ho J.M., Anekonda V.T., Thompson B.W., Zhu M., Curry R.W., Hwang B.H., et al. Hindbrain oxytocin receptors contribute to the effects of circulating oxytocin on food intake in male rats. Endocrinology 2014, 10.1210/en.2014-1148.
107. Mullis K., Kay K., Williams D.L. Oxytocin action in the ventral tegmental area affects sucrose intake. Brain Res. 2013.
108. Noble E.E., Billington C.J., Kotz C.M., Wang C. Oxytocin in the ventromedial hypothalamic nucleus reduces feeding and acutely increases energy expenditure. Am J Physiol Regul Integr Comp Physiol. 2014.
109. Rinaman L., Rothe E.E. GLP-1 receptor signaling contributes to anorexigenic effect of centrally administered oxytocin in rats. Am J Physiol Regul Integr Comp Physiol. 2002, 283:R99-106.
110. Yosten G.L., Samson W.K. The anorexigenic and hypertensive effects of nesfatin-1 are reversed by pretreatment with an oxytocin receptor antagonist. Am J Physiol Regul Integr Comp Physiol. 2010, 298:R1642-R1647.
111. Perlow M.J., Reppert S.M., Artman H.A., Fisher D.A., Self S.M., Robinson A.G. Oxytocin, vasopressin, and estrogen-stimulated neurophysin: daily patterns of concentration in cerebrospinal fluid. Science 1982, 216:1416-1418.
112. Olszewski P.K., Wirth M.M., Shaw T.J., Grace M.K., Billington C.J., Giraudo S.Q., et al. Role of alpha-MSH in the regulation of consummatory behavior: immunohistochemical evidence. Am J Physiol Regul Integr Comp Physiol. 2001, 281:R673-R680.
113. Liu H., Kishi T., Roseberry A.G., Cai X., Lee C.E., Montez J.M., et al. Transgenic mice expressing green fluorescent protein under the control of the melanocortin-4 receptor promoter. J Neurosci. 2003, 23:7143-7154.
114. Atasoy D., Betley J.N., Su H.H., Sternson S.M. Deconstruction of a neural circuit for hunger. Nature 2012, 488:172-177.
115. Pinol R.A., Bateman R., Mendelowitz D. Optogenetic approaches to characterize the long-range synaptic pathways from the hypothalamus to brain stem autonomic nuclei. J. Neurosci. Methods 2012, 210:238-246.
116. Pinol R.A., Jameson H., Popratiloff A., Lee N.H., Mendelowitz D. Visualization of oxytocin release that mediates paired pulse facilitation in hypothalamic pathways to brainstem autonomic neurons. PLoS One 2014, 9. e112138.
117. Singru P.S., Wittmann G., Farkas E., Zseli G., Fekete C., Lechan R.M. Refeeding-activated glutamatergic neurons in the hypothalamic paraventricular nucleus (PVN) mediate effects of melanocortin signaling in the nucleus tractus solitarius (NTS). Endocrinology 2012, 153:3804-3814.
118. Shah B.P., Vong L., Olson D.P., Koda S., Krashes M.J., Ye C., et al. MC4R-expressing glutamatergic neurons in the paraventricular hypothalamus regulate feeding and are synaptically connected to the parabrachial nucleus. Proc. Natl. Acad. Sci. U. S. A. 2014, 111:13193-13198.
119. Baskin D.G., Kim F., Gelling R.W., Russell B.J., Schwartz M.W., Morton G.J., et al. A new oxytocin-saporin cytotoxin for lesioning oxytocin-receptive neurons in the rat hindbrain. Endocrinology 2010, 151:4207-4213.
120. Blouet C., Jo Y.H., Li X., Schwartz G.J. Mediobasal hypothalamic leucine sensing regulates food intake through activation of a hypothalamus-brainstem circuit. J Neurosci. 2009, 29:8302-8311.
121. Amico J.A., Vollmer R.R., Cai H.M., Miedlar J.A., Rinaman L. Enhanced initial and sustained intake of sucrose solution in mice with an oxytocin gene deletion. Am J Physiol Regul Integr Comp Physiol. 2005, 289:R1798-R1806.
122. Herisson F.M., Brooks L.L., Waas J.R., Levine A.S., Olszewski P.K. Functional relationship between oxytocin and appetite for carbohydrates versus saccharin. Neuroreport 2014, 25:909-914.
123. Olszewski P.K., Klockars A., Olszewska A.M., Fredriksson R., Schioth H.B., Levine A.S. Molecular, immunohistochemical, and pharmacological evidence of oxytocin's role as inhibitor of carbohydrate but not fat intake. Endocrinology 2010, 151:4736-4744.
124. Olszewski P.K., Allen K., Levine A.S. Effect of oxytocin receptor blockade on appetite for sugar is modified by social context. Appetite 2015, 86:81-87.
125. Lee H.J., Caldwell H.K., Macbeth A.H., Tolu S.G., Young W.S. A conditional knockout mouse line of the oxytocin receptor. Endocrinology 2008, 149:3256-3263.
126. Aoyagi T., Birumachi J., Hiroyama M., Fujiwara Y., Sanbe A., Yamauchi J., et al. Alteration of glucose homeostasis in V1a vasopressin receptor-deficient mice. Endocrinology 2007, 148:2075-2084.
127. Enhorning S., Leosdottir M., Wallstrom P., Gullberg B., Berglund G., Wirfalt E., et al. Relation between human vasopressin 1a gene variance, fat intake, and diabetes. The American Journal of Clinical Nutrition 2009, 89:400-406.
128. Pei H., Sutton A.K., Burnett K.H., Fuller P.M., Olson D.P. AVP neurons in the paraventricular nucleus of the hypothalamus regulate feeding. Molecular Metabolism 2014, 3:209-215.
129. Langhans W., Delprete E., Scharrer E. Mechanisms of vasopressin's anorectic effect. Physiol. Behav. 1991, 49:169-176.
130. Yamashita M., Takayanagi Y., Yoshida M., Nishimori K., Kusama M., Onaka T. Involvement of prolactin-releasing peptide in the activation of oxytocin neurons in response to food intake. J. Neuroendocrinol. 2013, 25:455-465.
131. Wu Q., Howell M.P., Palmiter R.D. Ablation of neurons expressing agouti-related protein activates fos and gliosis in postsynaptic target regions. J Neurosci. 2008, 28:9218-9226.
132. Matsuzaki T., Iwasa T., Munkhzaya M., Tungalagsuvd A., Kawami T., Murakami M., et al. Developmental changes in hypothalamic oxytocin and oxytocin receptor mRNA expression and their sensitivity to fasting in male and female rats. International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience. 2015, 41C:105-109.
133. Lukas M., Bredewold R., Neumann I.D., Veenema A.H. Maternal separation interferes with developmental changes in brain vasopressin and oxytocin receptor binding in male rats. Neuropharmacology 2010, 58:78-87.
134. Kasahara Y., Sato K., Takayanagi Y., Mizukami H., Ozawa K., Hidema S., et al. Oxytocin receptor in the hypothalamus is sufficient to rescue normal thermoregulatory function in male oxytocin receptor knockout mice. Endocrinology 2013, 154:4305-4315.
135. Higa K.T., Mori E., Viana F.F., Morris M., Michelini L.C. Baroreflex control of heart rate by oxytocin in the solitary-vagal complex. Am J Physiol Regul Integr Comp Physiol. 2002, 282:R537-R545.
136. Backman S.B., Henry J.L. Effects of oxytocin and vasopressin on thoracic sympathetic preganglionic neurons in the cat. Brain Res. Bull. 1984, 13:679-684.
137. Armour J.A., Klassen G.A. Oxytocin modulation of intrathoracic sympathetic ganglionic neurons regulating the canine heart. Peptides 1990, 11:533-537.
138. Oldfield B.J., Giles M.E., Watson A., Anderson C., Colvill L.M., McKinley M.J. The neurochemical characterisation of hypothalamic pathways projecting polysynaptically to brown adipose tissue in the rat. Neuroscience 2002, 110:515-526.
139. Jansen A.S., Wessendorf M.W., Loewy A.D. Transneuronal labeling of CNS neuropeptide and monoamine neurons after pseudorabies virus injections into the stellate ganglion. Brain Res. 1995, 683:1-24.
140. Song C.K., Vaughan C.H., Keen-Rhinehart E., Harris R.B., Richard D., Bartness T.J. Melanocortin-4 receptor mRNA expressed in sympathetic outflow neurons to brown adipose tissue: neuroanatomical and functional evidence. Am J Physiol Regul Integr Comp Physiol. 2008, 295:R417-R428.
141. Fosgerau K., Raun K., Nilsson C., Dahl K., Wulff B.S. Novel alpha-MSH analog causes weight loss in obese rats and minipigs and improves insulin sensitivity. The Journal of Endocrinology 2014, 220:97-107.
142. Rosenbaum M., Kissileff H.R., Mayer L.E., Hirsch J., Leibel R.L. Energy intake in weight-reduced humans. Brain Res. 2010, 1350:95-102.
143. Rosenbaum M., Murphy E.M., Heymsfield S.B., Matthews D.E., Leibel R.L. Low dose leptin administration reverses effects of sustained weight-reduction on energy expenditure and circulating concentrations of thyroid hormones. J. Clin. Endocrinol. Metab. 2002, 87:2391-2394.
144. Schwartz A., Doucet E. Relative changes in resting energy expenditure during weight loss: a systematic review. Obesity reviews: an official journal of the International Association for the Study of Obesity 2010, 11:531-547.
145. Nedergaard J., Cannon B. The browning of white adipose tissue: some burning issues. Cell Metab. 2014, 20:396-407.
146. Fisher F.M., Kleiner S., Douris N., Fox E.C., Mepani R.J., Verdeguer F., et al. FGF21 regulates PGC-1alpha and browning of white adipose tissues in adaptive thermogenesis. Genes Dev. 2012, 26:271-281.
147. Wu J., Bostrom P., Sparks L.M., Ye L., Choi J.H., Giang A.H., et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 2012, 150:366-376.
148. Bostrom P., Wu J., Jedrychowski M.P., Korde A., Ye L., Lo J.C., et al. A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 2012, 481:463-468.
149. Shi H., Bartness T.J. Neurochemical phenotype of sympathetic nervous system outflow from brain to white fat. Brain Res. Bull. 2001, 54:375-385.
150. Stanley S., Pinto S., Segal J., Perez C.A., Viale A., DeFalco J., et al. Identification of neuronal subpopulations that project from hypothalamus to both liver and adipose tissue polysynaptically. Proc. Natl. Acad. Sci. U. S. A. 2010, 107:7024-7029.
151. Eckertova M., Ondrejcakova M., Krskova K., Zorad S., Jezova D. Subchronic treatment of rats with oxytocin results in improved adipocyte differentiation and increased gene expression of factors involved in adipogenesis. Br. J. Pharmacol. 2011, 162:452-463.
152. Monstein H.J., Grahn N., Truedsson M., Ohlsson B. Oxytocin and oxytocin-receptor mRNA expression in the human gastrointestinal tract: a polymerase chain reaction study. Regul. Pept. 2004, 119:39-44.
153. Wu C.L., Doong M.L., Wang P.S. Involvement of cholecystokinin receptor in the inhibition of gastrointestinal motility by oxytocin in ovariectomized rats. Eur. J. Pharmacol. 2008, 580:407-415.
154. Wu C.L., Hung C.R., Chang F.Y., Pau K.Y., Wang P.S. Pharmacological effects of oxytocin on gastric emptying and intestinal transit of a non-nutritive liquid meal in female rats. Naunyn Schmiedeberg's Arch. Pharmacol. 2003, 367:406-413.
155. Ring R.H., Malberg J.E., Potestio L., Ping J., Boikess S., Luo B., et al. Anxiolytic-like activity of oxytocin in male mice: behavioral and autonomic evidence, therapeutic implications. Psychopharmacology 2006, 185:218-225.
156. Ring R.H., Schechter L.E., Leonard S.K., Dwyer J.M., Platt B.J., Graf R., et al. Receptor and behavioral pharmacology of WAY-267464, a non-peptide oxytocin receptor agonist. Neuropharmacology 2010, 58:69-77.
157. Borg, J., Simren, M., Ohlsson, B. Oxytocin reduces satiety scores without affecting the volume of nutrient intake or gastric emptying rate in healthy subjects. Neurogastroenterology and motility: the official journal of the European Gastrointestinal Motility Society 2011,23:56-61, e5.
158. McCann M.J., Verbalis J.G., Stricker E.M. LiCl and CCK inhibit gastric emptying and feeding and stimulate OT secretion in rats. Am. J. Phys. 1989, 256:R463-R468.
159. Li L., Kong X., Liu H., Liu C. Systemic oxytocin and vasopressin excite gastrointestinal motility through oxytocin receptor in rabbits. Neurogastroenterology and motility: the official journal of the European Gastrointestinal Motility Society 2007, 19:839-844.
160. Welch M.G., Margolis K.G., Li Z., Gershon M.D. Oxytocin regulates gastrointestinal motility, inflammation, macromolecular permeability, and mucosal maintenance in mice. Am. J. Physiol. Gastrointest. Liver Physiol. 2014, 307:G848-G862.
161. Mens W.B., Witter A., van Wimersma Greidanus T.B. Penetration of neurohypophyseal hormones from plasma into cerebrospinal fluid (CSF): half-times of disappearance of these neuropeptides from CSF. Brain Res. 1983, 262:143-149.
162. Neumann I.D., Maloumby R., Beiderbeck D.I., Lukas M., Landgraf R. Increased brain and plasma oxytocin after nasal and peripheral administration in rats and mice. Psychoneuroendocrinology 2013, 38:1985-1993.
163. Kendrick K.M., Keverne E.B., Baldwin B.A., Sharman D.F. Cerebrospinal fluid levels of acetylcholinesterase, monoamines and oxytocin during labour, parturition, vaginocervical stimulation, lamb separation and suckling in sheep. Neuroendocrinology 1986, 44:149-156.
164. Flanagan L.M., Olson B.R., Sved A.F., Verbalis J.G., Stricker E.M. Gastric motility in conscious rats given oxytocin and an oxytocin antagonist centrally. Brain Res. 1992, 578:256-260.
165. Rogers R.C., Hermann G.E. Oxytocin, oxytocin antagonist, TRH, and hypothalamic paraventricular nucleus stimulation effects on gastric motility. Peptides 1987, 8:505-513.
166. Vila G., Riedl M., Resl M., van der Lely A.J., Hofland L.J., Clodi M., et al. Systemic administration of oxytocin reduces basal and lipopolysaccharide-induced ghrelin levels in healthy men. The Journal of Endocrinology 2009, 203:175-179.
167. Burri A., Heinrichs M., Schedlowski M., Kruger T.H. The acute effects of intranasal oxytocin administration on endocrine and sexual function in males. Psychoneuroendocrinology 2008, 33:591-600.
168. Striepens N., Kendrick K.M., Hanking V., Landgraf R., Wullner U., Maier W., et al. Elevated cerebrospinal fluid and blood concentrations of oxytocin following its intranasal administration in humans. Sci. Rep. 2013, 3:3440.
169. Gimpl G., Klein U., Reilander H., Fahrenholz F. Expression of the human oxytocin receptor in baculovirus-infected insect cells: high-affinity binding is induced by a cholesterol-cyclodextrin complex. Biochemistry 1995, 34:13794-13801.
170. Insel T.R., Winslow J.T., Witt D.M. Homologous regulation of brain oxytocin receptors. Endocrinology 1992, 130:2602-2608.
171. Peters S., Slattery D.A., Uschold-Schmidt N., Reber S.O., Neumann I.D. Dose-dependent effects of chronic central infusion of oxytocin on anxiety, oxytocin receptor binding and stress-related parameters in mice. Psychoneuroendocrinology 2014, 42:225-236.
172. Kharitonenkov A., Wroblewski V.J., Koester A., Chen Y.F., Clutinger C.K., Tigno X.T., et al. The metabolic state of diabetic monkeys is regulated by fibroblast growth factor-21. Endocrinology 2007, 148:774-781.
173. Veniant M.M., Komorowski R., Chen P., Stanislaus S., Winters K., Hager T., et al. Long-acting FGF21 has enhanced efficacy in diet-induced obese mice and in obese rhesus monkeys. Endocrinology 2012, 153:4192-4203.
174. Barnhart K.F., Christianson D.R., Hanley P.W., Driessen W.H., Bernacky B.J., Baze W.B., et al. A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys. Sci. Transl. Med. 2011, 3(108):ra12.
175. Kievit P., Halem H., Marks D.L., Dong J.Z., Glavas M.M., Sinnayah P., et al. Chronic treatment with a melanocortin-4 receptor agonist causes weight loss, reduces insulin resistance, and improves cardiovascular function in diet-induced obese rhesus macaques. Diabetes 2013, 62:490-497.
176. Calcagnoli F., Meyer N., de Boer S.F., Althaus M., Koolhaas J.M. Chronic enhancement of brain oxytocin levels causes enduring anti-aggressive and pro-social explorative behavioral effects in male rats. Horm. Behav. 2014, 65:427-433.
177. Petersson M., Alster P., Lundeberg T., Uvnas-Moberg K. Oxytocin causes a long-term decrease of blood pressure in female and male rats. Physiol. Behav. 1996, 60:1311-1315.
178. Carson D.S., Hunt G.E., Guastella A.J., Barber L., Cornish J.L., Arnold J.C., et al. Systemically administered oxytocin decreases methamphetamine activation of the subthalamic nucleus and accumbens core and stimulates oxytocinergic neurons in the hypothalamus. Addict. Biol. 2010, 15:448-463.
179. Hicks C., Jorgensen W., Brown C., Fardell J., Koehbach J., Gruber C.W., et al. The nonpeptide oxytocin receptor agonist WAY 267,464: receptor-binding profile, prosocial effects and distribution of c-Fos expression in adolescent rats. J. Neuroendocrinol. 2012, 24:1012-1029.
180. Kendrick K.M. Oxytocin, motherhood and bonding. Exp. Physiol. 2000, 85. Spec No:111S-24S.
181. Banks W.A., During M.J., Niehoff M.L. Brain uptake of the glucagon-like peptide-1 antagonist exendin(9-39) after intranasal administration. The Journal of Pharmacology and Experimental Therapeutics 2004, 309:469-475.
182. Levin B.E., Dunn-Meynell A.A. Chronic exercise lowers the defended body weight gain and adiposity in diet-induced obese rats. Am J Physiol Regul Integr Comp Physiol. 2004, 286:R771-R778.
183. Yu Y., Deng C., Huang X.F. Obese reversal by a chronic energy restricted diet leaves an increased Arc NPY/AgRP, but no alteration in POMC/CART, mRNA expression in diet-induced obese mice. Behav. Brain Res. 2009, 205:50-56.
184. Tateya S., Kim F., Tamori Y. Recent advances in obesity-induced inflammation and insulin resistance. Front. Endocrinol. 2013, 4:93.
185. Kim F., Pham M., Maloney E., Rizzo N.O., Morton G.J., Wisse B.E., et al. Vascular inflammation, insulin resistance, and reduced nitric oxide production precede the onset of peripheral insulin resistance. Arterioscler. Thromb. Vasc. Biol. 2008, 28:1982-1988.
186. Thaler J.P., Yi C.X., Schur E.A., Guyenet S.J., Hwang B.H., Dietrich M.O., et al. Obesity is associated with hypothalamic injury in rodents and humans. J. Clin. Invest. 2012, 122:153-162.
187. Nation D.A., Szeto A., Mendez A.J., Brooks L.G., Zaias J., Herderick E.E., et al. Oxytocin attenuates atherosclerosis and adipose tissue inflammation in socially isolated ApoE-/- mice. Psychosom. Med. 2010, 72:376-382.
188. Szeto A., Rossetti M.A., Mendez A.J., Noller C.M., Herderick E.E., Gonzales J.A., et al. Oxytocin administration attenuates atherosclerosis and inflammation in Watanabe Heritable Hyperlipidemic rabbits. Psychoneuroendocrinology 2013, 38:685-693.
189. Parent A.S., Rasier G., Matagne V., Lomniczi A., Lebrethon M.C., Gerard A., et al. Oxytocin facilitates female sexual maturation through a glia-to-neuron signaling pathway. Endocrinology 2008, 149:1358-1365.
190. Vankrieken L., Godart A., Thomas K. Oxytocin determination by radioimmunoassay. Gynecol. Obstet. Investig. 1983, 16:180-185.
191. Muttenthaler M., Andersson A., de Araujo A.D., Dekan Z., Lewis R.J., Alewood P.F. Modulating oxytocin activity and plasma stability by disulfide bond engineering. J. Med. Chem. 2010, 53:8585-8596.
192. Stymiest J.L., Mitchell B.F., Wong S., Vederas J.C. Synthesis of oxytocin analogues with replacement of sulfur by carbon gives potent antagonists with increased stability. The Journal of Organic Chemistry 2005, 70:7799-7809.
193. Wood S.P., Tickle I.J., Treharne A.M., Pitts J.E., Mascarenhas Y., Li J.Y., et al. Crystal structure analysis of deamino-oxytocin: conformational flexibility and receptor binding. Science 1986, 232:633-636.
194. Sweeney G., Holbrook A.M., Levine M., Yip M., Alfredsson K., Cappi S., et al. Pharmacokinetics of carbetocin, a long-acting oxytocin analogue, in non pregnant women. Curr. Ther. Res. Clin. Exper. 1990, 47:528-539.
195. Hunter D.J., Schulz P., Wassenaar W. Effect of carbetocin, a long-acting oxytocin analog on the postpartum uterus. Clin. Pharmacol. Ther. 1992, 52:60-67.
196. Chelikani P.K., Haver A.C., Reeve J.R., Keire D.A., Reidelberger R.D. Daily, intermittent intravenous infusion of peptide YY(3-36) reduces daily food intake and adiposity in rats. Am J Physiol Regul Integr Comp Physiol. 2006, 290:R298-R305.
197. Chelikani P.K., Haver A.C., Reidelberger R.D. Effects of intermittent intraperitoneal infusion of salmon calcitonin on food intake and adiposity in obese rats. Am J Physiol Regul Integr Comp Physiol. 2007, 293:R1798-R1808.
198. Contreras G.A., Lee Y.H., Mottillo E.P., Granneman J.G. Inducible brown adipocytes in subcutaneous inguinal white fat: the role of continuous sympathetic stimulation. Am J Physiol Endocrinol Metab. 2014, 307:E793-E799.
199. Henry, K. E., Elfers, C. T., Burke, R. M., Chepurny, O. G., Holz, G. G., Blevins, J. E., et al. Vitamin B conjugation of peptide-YY decreases food intake compared to native peptide-YY upon subcutaneous administration in male rats. Endocrinology. 2015:en20141825.
200. Bray G.A., Popkin B.M. Dietary fat intake does affect obesity!. The American Journal of Clinical Nutrition 1998, 68:1157-1173.
201. Teng B.L., Nonneman R.J., Agster K.L., Nikolova V.D., Davis T.T., Riddick N.V., et al. Prosocial effects of oxytocin in two mouse models of autism spectrum disorders. Neuropharmacology 2013, 72:187-196.
202. Dirkx E., van Eys G.J., Schwenk R.W., Steinbusch L.K., Hoebers N., Coumans W.A., et al. Protein kinase-D1 overexpression prevents lipid-induced cardiac insulin resistance. J. Mol. Cell. Cardiol. 2014, 76:208-217.
203. Gault V.A., Bhat V.K., Irwin N., Flatt P.R. A novel glucagon-like peptide-1 (GLP-1)/glucagon hybrid peptide with triple-acting agonist activity at glucose-dependent insulinotropic polypeptide, GLP-1, and glucagon receptors and therapeutic potential in high fat-fed mice. The Journal of Biological Chemistry 2013, 288:35581-35591.
204. Irwin N., Frizelle P., O'Harte F.P., Flatt P.R. (pGlu-Gln)-CCK-8[mPEG]: a novel, long-acting, mini-PEGylated cholecystokinin (CCK) agonist that improves metabolic status in dietary-induced diabetes. Biochim. Biophys. Acta 2013, 1830:4009-4016.
205. Kriegeskorte A., Block D., Drescher M., Windmuller N., Mellmann A., Baum C., et al. Inactivation of thyA in Staphylococcus aureus attenuates virulence and has a strong impact on metabolism and virulence gene expression. MBio. 2014, 5. e01447-14.
206. van Blitterswijk M., Mullen B., Wojtas A., Heckman M.G., Diehl N.N., Baker M.C., et al. Genetic modifiers in carriers of repeat expansions in the C9ORF72 gene. Mol. Neurodegener. 2014, 9:38.
207. Born J., Lange T., Kern W., McGregor G.P., Bickel U., Fehm H.L. Sniffing neuropeptides: a transnasal approach to the human brain. Nat. Neurosci. 2002, 5:514-516.
208. Chang S.W., Barter J.W., Ebitz R.B., Watson K.K., Platt M.L. Inhaled oxytocin amplifies both vicarious reinforcement and self reinforcement in rhesus macaques (Macaca mulatta). Proc. Natl. Acad. Sci. U. S. A. 2012, 109:959-964.
209. Gossen A., Hahn A., Westphal L., Prinz S., Schultz R.T., Grunder G., et al. Oxytocin plasma concentrations after single intranasal oxytocin administration - a study in healthy men. Neuropeptides 2012, 46:211-215.
210. Ludwig M., Tobin V.A., Callahan M.F., Papadaki E., Becker A., Engelmann M., et al. Intranasal application of vasopressin fails to elicit changes in brain immediate early gene expression, neural activity and behavioural performance of rats. J. Neuroendocrinol. 2013, 25:655-667.
211. Moos F., Richard P. Paraventricular and supraoptic bursting oxytocin cells in rat are locally regulated by oxytocin and functionally related. J. Physiol. 1989, 408:1-18.
212. Yamashita H., Okuya S., Inenaga K., Kasai M., Uesugi S., Kannan H., et al. Oxytocin predominantly excites putative oxytocin neurons in the rat supraoptic nucleus in vitro. Brain Res. 1987, 416:364-368.
213. Carson D.S., Cornish J.L., Guastella A.J., Hunt G.E., McGregor I.S. Oxytocin decreases methamphetamine self-administration, methamphetamine hyperactivity, and relapse to methamphetamine-seeking behaviour in rats. Neuropharmacology 2010, 58:38-43.
214. Dal Monte O., Noble P.L., Turchi J., Cummins A., Averbeck B.B. CSF and blood oxytocin concentration changes following intranasal delivery in macaque. PLoS One 2014, 9. e103677.
215. Kirkpatrick M.G., Francis S.M., Lee R., de Wit H., Jacob S. Plasma oxytocin concentrations following MDMA or intranasal oxytocin in humans. Psychoneuroendocrinology 2014, 46:23-31.
216. Kuo J.J., Silva A.A., Hall J.E. Hypothalamic melanocortin receptors and chronic regulation of arterial pressure and renal function. Hypertension 2003, 41:768-774.
217. Skibicka K.P., Grill H.J. Hypothalamic and hindbrain melanocortin receptors contribute to the feeding, thermogenic, and cardiovascular action of melanocortins. Endocrinology 2009, 150:5351-5361.
218. Greenfield J.R., Miller J.W., Keogh J.M., Henning E., Satterwhite J.H., Cameron G.S., et al. Modulation of blood pressure by central melanocortinergic pathways. N. Engl. J. Med. 2009, 360:44-52.
219. Nguyen N.T., Magno C.P., Lane K.T., Hinojosa M.W., Lane J.S. Association of hypertension, diabetes, dyslipidemia, and metabolic syndrome with obesity: findings from the National Health and Nutrition Examination Survey, 1999 to 2004. J. Am. Coll. Surg. 2008, 207:928-934.
220. MacDonald E., Dadds M.R., Brennan J.L., Williams K., Levy F., Cauchi A.J. A review of safety, side-effects and subjective reactions to intranasal oxytocin in human research. Psychoneuroendocrinology 2011, 36:1114-1126.
221. Hicks C., Ramos L., Reekie T., Misagh G.H., Narlawar R., Kassiou M., et al. Body temperature and cardiac changes induced by peripherally administered oxytocin, vasopressin and the non-peptide oxytocin receptor agonist WAY 267,464: a biotelemetry study in rats. Br. J. Pharmacol. 2014, 171:2868-2887.
222. Yang Z., Han D., Coote J.H. Cardiac sympatho-excitatory action of PVN-spinal oxytocin neurons. Autonomic Neuroscience: Basic & Clinical 2009, 147:80-85.
223. Yosten G.L., Samson W.K. Neural circuitry underlying the central hypertensive action of nesfatin-1: melanocortins, corticotropin-releasing hormone, and oxytocin. Am J Physiol Regul Integr Comp Physiol. 2014, 306:R722-R727.
224. Gutkowska J., Jankowski M. Oxytocin revisited: its role in cardiovascular regulation. J. Neuroendocrinol. 2012, 24:599-608.
225. Petersson M. Cardiovascular effects of oxytocin. Prog. Brain Res. 2002, 139:281-288.
226. Modi M.E., Connor-Stroud F., Landgraf R., Young L.J., Parr L.A. Aerosolized oxytocin increases cerebrospinal fluid oxytocin in rhesus macaques. Psychoneuroendocrinology 2014, 45:49-57.
227. Goldman M.B., Gomes A.M., Carter C.S., Lee R. Divergent effects of two different doses of intranasal oxytocin on facial affect discrimination in schizophrenic patients with and without polydipsia. Psychopharmacology 2011, 216:101-110.
228. Rubin L.H., Carter C.S., Drogos L., Pournajafi-Nazarloo H., Sweeney J.A., Maki P.M. Peripheral oxytocin is associated with reduced symptom severity in schizophrenia. Schizophr. Res. 2010, 124:13-21.
229. Alvares G.A., Hickie I.B., Guastella A.J. Acute effects of intranasal oxytocin on subjective and behavioral responses to social rejection. Exp. Clin. Psychopharmacol. 2010, 18:316-321.
230. Chan E.W., He Y., Chui C.S., Wong A.Y., Lau W.C., Wong I.C. Efficacy and safety of lorcaserin in obese adults: a meta-analysis of 1-year randomized controlled trials (RCTs) and narrative review on short-term RCTs. Obesity reviews: an official journal of the International Association for the Study of Obesity 2013, 14:383-392.
231. Yanovski S.Z., Yanovski J.A. Long-term drug treatment for obesity: a systematic and clinical review. JAMA: the journal of the American Medical Association 2014, 311:74-86.
232. Fuchs A.R., Fuchs F., Husslein P., Soloff M.S., Fernstrom M.J. Oxytocin receptors and human parturition: a dual role for oxytocin in the initiation of labor. Science 1982, 215:1396-1398.
233. Pound L.D., Kievit P., Grove K.L. The nonhuman primate as a model for type 2 diabetes. Current Opinion in Endocrinology, Diabetes, and Obesity 2014, 21:89-94.
234. Salazar M., Hu B.B., Vazquez J., Wintz R.L., Varon J. Exogenous vasopressin-induced hyponatremia in patients with vasodilatory shock: two case reports and literature review. J. Intensive Care Med. 2013.
235. Manning M., Misicka A., Olma A., Bankowski K., Stoev S., Chini B., et al. Oxytocin and vasopressin agonists and antagonists as research tools and potential therapeutics. J. Neuroendocrinol. 2012, 24:609-628.
236. Palm C., Reimann D., Gross P. The role of V2 vasopressin antagonists in hyponatremia. Cardiovasc. Res. 2001, 51:403-408.
237. Schrier R.W., Gross P., Gheorghiade M., Berl T., Verbalis J.G., Czerwiec F.S., et al. Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N. Engl. J. Med. 2006, 355:2099-2112.
238. Devost D., Zingg H.H. Homo- and hetero-dimeric complex formations of the human oxytocin receptor. J. Neuroendocrinol. 2004, 16:372-377.
239. Viero C., Shibuya I., Kitamura N., Verkhratsky A., Fujihara H., Katoh A., et al. REVIEW: oxytocin: crossing the bridge between basic science and pharmacotherapy. CNS Neurosci. Ther. 2010, 16:e138-e156.
240. Bales K.L., Perkeybile A.M., Conley O.G., Lee M.H., Guoynes C.D., Downing G.M., et al. Chronic intranasal oxytocin causes long-term impairments in partner preference formation in male prairie voles. Biol. Psychiatry 2012, 4.
241. Bales K.L., Solomon M., Jacob S., Crawley J.N., Silverman J.L., Larke R.H., et al. Long-term exposure to intranasal oxytocin in a mouse autism model. Translational Psychiatry 2014, 4. e480.