Skip to main content

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

  • Review Article
  • Published:

The effects of oxytocin on eating behaviour and metabolism in humans

Key Points

  • Animal studies indicate that oxytocin is a potent regulator of caloric intake and metabolism; clinical investigations are beginning to translate these findings to humans

  • A single dose of intranasal oxytocin reduces caloric intake in men, particularly of more palatable foods, and these effects could be increased in men with obesity

  • Intranasal oxytocin acutely increases the use of fat as a fuel for the body, but effects of oxytocin in promoting energy expenditure have not been demonstrated in humans

  • An 8-week pilot study of intranasal oxytocin in a small group of men and women with overweight or obesity led to substantial weight loss

  • Independently of effects on body weight, oxytocin might improve glucose homeostasis, but the data are conflicting

  • Pathways that involve oxytocin offer novel therapeutic targets for obesity and metabolic disease

Abstract

Oxytocin, a hypothalamic hormone that is secreted directly into the brain and enters the peripheral circulation through the posterior pituitary gland, regulates a range of physiologic processes, including eating behaviour and metabolism. In rodents and nonhuman primates, chronic oxytocin administration leads to sustained weight reduction by reducing food intake, increasing energy expenditure and inducing lipolysis. Oxytocin might improve glucose homeostasis, independently of its effects on weight. Clinical studies are beginning to translate these important preclinical findings to humans. This Review describes key data linking oxytocin to eating behaviour and metabolism in humans. For example, a single intranasal dose of oxytocin can reduce caloric intake, increase fat oxidation and improve insulin sensitivity in men. Furthermore, a pilot study of 8 weeks of oxytocin treatment in adults with obesity or overweight led to substantial weight loss. Together, these data support further investigation of interventions that target pathways involving oxytocin as potential therapeutics in metabolic disorders, including obesity and diabetes mellitus. Therapeutic considerations and areas for further research are also discussed.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1: Hypothesized mechanisms underlying the effects of oxytocin on caloric intake.
Figure 2: Proposed model of the effects of oxytocin on metabolic parameters.

Similar content being viewed by others

References

  1. Tribollet, E., Barberis, C., Dubois-Dauphin, M. & Dreifuss, J. J. Localization and characterization of binding sites for vasopressin and oxytocin in the brain of the guinea pig. Brain Res. 589, 15–23 (1992).

    Article  CAS  PubMed  Google Scholar 

  2. Sabatier, N., Rowe, I. & Leng, G. Central release of oxytocin and the ventromedial hypothalamus. Biochem. Soc. Trans. 35, 1247–1251 (2007).

    Article  CAS  PubMed  Google Scholar 

  3. Maejima, Y. et al. Oxytocinergic circuit from paraventricular and supraoptic nuclei to arcuate POMC neurons in hypothalamus. FEBS Lett. 588, 4404–4412 (2014).

    Article  CAS  PubMed  Google Scholar 

  4. 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 151, 2276–2286 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Ross, H. E. et al. Characterization of the oxytocin system regulating affiliative behavior in female prairie voles. Neuroscience 162, 892–903 (2009).

    Article  PubMed  CAS  Google Scholar 

  6. Rinaman, L. Oxytocinergic inputs to the nucleus of the solitary tract and dorsal motor nucleus of the vagus in neonatal rats. J. Comp. Neurol. 399, 101–109 (1998).

    Article  CAS  PubMed  Google Scholar 

  7. 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. 205, 260–272 (1982).

    Article  CAS  PubMed  Google Scholar 

  8. Blevins, J. E. & Baskin, D. G. Translational and therapeutic potential of oxytocin as an anti-obesity strategy: insights from rodents, nonhuman primates and humans. Physiol. Behav. 152, 438–449 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Ohlsson, B., Truedsson, M., Djerf, P. & Sundler, F. Oxytocin is expressed throughout the human gastrointestinal tract. Regul. Pept. 135, 7–11 (2006).

    Article  CAS  PubMed  Google Scholar 

  10. Qin, J. et al. Oxytocin receptor expressed on the smooth muscle mediates the excitatory effect of oxytocin on gastric motility in rats. Neurogastroenterol. Motil. 21, 430–438 (2009).

    Article  CAS  PubMed  Google Scholar 

  11. Feng, M. et al. Estradiol upregulates the expression of oxytocin receptor in colon in rats. Am. J. Physiol. Endocrinol. Metab. 296, E1059–E1066 (2009).

    Article  CAS  PubMed  Google Scholar 

  12. Welch, M. G. et al. Expression and developmental regulation of oxytocin (OT) and oxytocin receptors (OTR) in the enteric nervous system (ENS) and intestinal epithelium. J. Comp. Neurol. 512, 256–270 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Ho, J. M. et al. Hindbrain oxytocin receptors contribute to the effects of circulating oxytocin on food intake in male rats. Endocrinology 155, 2845–2857 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Blevins, J. E. 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. 308, R431–R438 (2015).

    Article  CAS  PubMed  Google Scholar 

  15. Iwasaki, Y. 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. 308, R360–R369 (2015).

    Article  CAS  PubMed  Google Scholar 

  16. Lee, M. R. et al. Oxytocin by intranasal and intravenous routes reaches the cerebrospinal fluid in rhesus macaques: determination using a novel oxytocin assay. Mol. Psychiatry http://dx.doi.org/10.1038/mp.2017.27 (2017).

  17. Zhang, G. & Cai, D. Circadian intervention of obesity development via resting-stage feeding manipulation or oxytocin treatment. Am. J. Physiol. Endocrinol. Metab. 301, E1004–E1012 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Deblon, N. et al. Mechanisms of the anti-obesity effects of oxytocin in diet-induced obese rats. PLoS ONE 6, e25565 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. 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 122, 155–167 (2003).

    Article  CAS  PubMed  Google Scholar 

  20. Yoshida, M. et al. Evidence that oxytocin exerts anxiolytic effects via oxytocin receptor expressed in serotonergic neurons in mice. J. Neurosci. 29, 2259–2271 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Wrobel, L. et al. Distribution and identity of neurons expressing the oxytocin receptor in the mouse spinal cord. Neurosci. Lett. 495, 49–54 (2011).

    Article  CAS  PubMed  Google Scholar 

  22. Hidema, S. et al. Generation of Oxtr cDNA(HA)-Ires-Cre mice for gene expression in an oxytocin receptor specific manner. J. Cell. Biochem. 117, 1099–1111 (2016).

    Article  CAS  PubMed  Google Scholar 

  23. Peris, J. et al. Oxytocin receptors are expressed on dopamine and glutamate neurons in the mouse ventral tegmental area that project to nucleus accumbens and other mesolimbic targets. J. Comp. Neurol. 525, 1094–1108 (2017).

    Article  CAS  PubMed  Google Scholar 

  24. Vaccari, C., Lolait, S. J. & Ostrowski, N. L. Comparative distribution of vasopressin V1b and oxytocin receptor messenger ribonucleic acids in brain. Endocrinology 139, 5015–5033 (1998).

    Article  CAS  PubMed  Google Scholar 

  25. van Leeuwen, F. W., van Heerikhuize, J., van der Meulen, G. & Wolters, P. Light microscopic autoradiographic localization of [3H]oxytocin binding sites in the rat brain, pituitary and mammary gland. Brain Res. 359, 320–325 (1985).

    Article  CAS  PubMed  Google Scholar 

  26. Altirriba, J. et al. Divergent effects of oxytocin treatment of obese diabetic mice on adiposity and diabetes. Endocrinology 155, 4189–4201 (2014).

    Article  CAS  PubMed  Google Scholar 

  27. Gajdosechova, L. et al. Hypooxytocinaemia in obese Zucker rats relates to oxytocin degradation in liver and adipose tissue. J. Endocrinol. 220, 333–343 (2014).

    Article  CAS  PubMed  Google Scholar 

  28. Muchmore, D. B., Little, S. A. & de Haen, C. A dual mechanism of action of ocytocin in rat epididymal fat cells. J. Biol. Chem. 256, 365–372 (1981).

    CAS  PubMed  Google Scholar 

  29. Suzuki, M., Honda, Y., Li, M. Z., Masuko, S. & Murata, Y. The localization of oxytocin receptors in the islets of Langerhans in the rat pancreas. Regul. Pept. 183, 42–45 (2013).

    Article  CAS  PubMed  Google Scholar 

  30. Antoni, F. A. Oxytocin receptors in rat adenohypophysis: evidence from radioligand binding studies. Endocrinology 119, 2393–2395 (1986).

    Article  CAS  PubMed  Google Scholar 

  31. Gimpl, G. & Fahrenholz, F. The oxytocin receptor system: structure, function, and regulation. Physiol. Rev. 81, 629–683 (2001).

    Article  CAS  PubMed  Google Scholar 

  32. Kasahara, Y., Takayanagi, Y., Kawada, T., Itoi, K. & Nishimori, K. Impaired thermoregulatory ability of oxytocin-deficient mice during cold-exposure. Biosci. Biotechnol. Biochem. 71, 3122–3126 (2007).

    Article  CAS  PubMed  Google Scholar 

  33. Takayanagi, Y. et al. Oxytocin receptor-deficient mice developed late-onset obesity. Neuroreport 19, 951–955 (2008).

    Article  CAS  PubMed  Google Scholar 

  34. Camerino, C. Low sympathetic tone and obese phenotype in oxytocin-deficient mice. Obesity 17, 980–984 (2009).

    Article  CAS  PubMed  Google Scholar 

  35. Kublaoui, B. M., Gemelli, T., Tolson, K. P., Wang, Y. & Zinn, A. R. Oxytocin deficiency mediates hyperphagic obesity of Sim1 haploinsufficient mice. Mol. Endocrinol. 22, 1723–1734 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Zhang, H. et al. Treatment of obesity and diabetes using oxytocin or analogs in patients and mouse models. PLoS ONE 8, e61477 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Maejima, Y. et al. Peripheral oxytocin treatment ameliorates obesity by reducing food intake and visceral fat mass. Aging 3, 1169–1177 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Morton, G. J. et al. Peripheral oxytocin suppresses food intake and causes weight loss in diet-induced obese rats. Am. J. Physiol. Endocrinol. Metabol. 302, E134–E144 (2012).

    Article  CAS  Google Scholar 

  39. McCullough, M. E., Churchland, P. S. & Mendez, A. J. Problems with measuring peripheral oxytocin: can the data on oxytocin and human behavior be trusted? Neurosci. Biobehav. Rev. 37, 1485–1492 (2013).

    Article  CAS  PubMed  Google Scholar 

  40. Leng, G. & Sabatier, N. Measuring oxytocin and vasopressin: bioassays, immunoassays and random numbers. J. Neuroendocrinol. http://dx.doi.org/10.1111/jne.12413 (2016).

  41. Szeto, A. et al. Evaluation of enzyme immunoassay and radioimmunoassay methods for the measurement of plasma oxytocin. Psychosom. Med. 73, 393–400 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Brandtzaeg, O. K. et al. Proteomics tools reveal startlingly high amounts of oxytocin in plasma and serum. Sci. Rep. 6, 31693 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Sabatier, N. et al. Alpha-melanocyte-stimulating hormone stimulates oxytocin release from the dendrites of hypothalamic neurons while inhibiting oxytocin release from their terminals in the neurohypophysis. J. Neurosci. 23, 10351–10358 (2003).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Amico, J. A., Challinor, S. M. & Cameron, J. L. Pattern of oxytocin concentrations in the plasma and cerebrospinal fluid of lactating rhesus monkeys (Macaca mulatta): evidence for functionally independent oxytocinergic pathways in primates. J. Clin. Endocrinol. Metab. 71, 1531–1535 (1990).

    Article  CAS  PubMed  Google Scholar 

  45. Neumann, I., Landgraf, R., Takahashi, Y., Pittman, Q. J. & Russell, J. A. Stimulation of oxytocin release within the supraoptic nucleus and into blood by CCK-8. Am. J. Physiol. 267, R1626–R1631 (1994).

    CAS  PubMed  Google Scholar 

  46. Ivanyi, T., Wiegant, V. M. & de Wied, D. Differential effects of emotional and physical stress on the central and peripheral secretion of neurohypophysial hormones in male rats. Life Sci. 48, 1309–1316 (1991).

    Article  CAS  PubMed  Google Scholar 

  47. Heller, H. & Zaimis, E. J. The antidiuretic and oxytocic hormones in the posterior pituitary glands of newborn infants and adults. J. Physiol. 109, 162–169 (1949).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Leng, G. & Ludwig, M. Intranasal oxytocin: myths and delusions. Biol. Psychiatry 79, 243–250 (2016).

    Article  CAS  PubMed  Google Scholar 

  49. Hicks, C. et al. Regional c-Fos expression induced by peripheral oxytocin administration is prevented by the vasopressin 1A receptor antagonist SR49059. Brain Res. Bull. 127, 208–218 (2016).

    Article  CAS  PubMed  Google Scholar 

  50. Arletti, R., Benelli, A. & Bertolini, A. Influence of oxytocin on feeding behavior in the rat. Peptides 10, 89–93 (1989).

    Article  CAS  PubMed  Google Scholar 

  51. Lawson, E. A. et al. Oxytocin reduces caloric intake in men. Obesity 23, 950–956 (2015).

    Article  CAS  PubMed  Google Scholar 

  52. Ott, V. et al. Oxytocin reduces reward-driven food intake in humans. Diabetes 62, 3418–3425 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. 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. 289, R1798–R1806 (2005).

    Article  CAS  PubMed  Google Scholar 

  54. Sclafani, A., Rinaman, L., Vollmer, R. R. & Amico, J. A. Oxytocin knockout mice demonstrate enhanced intake of sweet and nonsweet carbohydrate solutions. Am. J. Physiol. Regul. Integr. Comp. Physiol. 292, R1828–R1833 (2007).

    Article  PubMed  CAS  Google Scholar 

  55. Miedlar, J. A., Rinaman, L., Vollmer, R. R. & Amico, J. A. Oxytocin gene deletion mice overconsume palatable sucrose solution but not palatable lipid emulsions. Am. J. Physiol. Regul. Integr. Comp. Physiol. 293, R1063–R1068 (2007).

    Article  CAS  PubMed  Google Scholar 

  56. Mullis, K., Kay, K. & Williams, D. L. Oxytocin action in the ventral tegmental area affects sucrose intake. Brain Res. 1513, 85–91 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Wu, C. L. et al. Involvement of cholecystokinin receptor in the inhibition of gastric emptying by oxytocin in male rats. Pflugers Arch. 445, 187–193 (2002).

    Article  CAS  PubMed  Google Scholar 

  58. 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 Schmiedebergs Arch. Pharmacol. 367, 406–413 (2003).

    Article  CAS  PubMed  Google Scholar 

  59. Rogers, R. C. & Hermann, G. E. Oxytocin, oxytocin antagonist, TRH, and hypothalamic paraventricular nucleus stimulation effects on gastric motility. Peptides 8, 505–513 (1987).

    Article  CAS  PubMed  Google Scholar 

  60. 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. 578, 256–260 (1992).

    Article  CAS  PubMed  Google Scholar 

  61. 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. 283, R99–R106 (2002).

    Article  CAS  PubMed  Google Scholar 

  62. 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. 580, 407–415 (2008).

    Article  CAS  PubMed  Google Scholar 

  63. Demitrack, M. A. et al. CSF oxytocin in anorexia nervosa and bulimia nervosa: clinical and pathophysiologic considerations. Am. J. Psychiatry 147, 882–886 (1990).

    Article  CAS  PubMed  Google Scholar 

  64. Frank, G. K., Kaye, W. H., Altemus, M. & Greeno, C. G. CSF oxytocin and vasopressin levels after recovery from bulimia nervosa and anorexia nervosa, bulimic subtype. Biol. Psychiatry 48, 315–318 (2000).

    Article  CAS  PubMed  Google Scholar 

  65. Chiodera, P. et al. Effect of estrogen or insulin-induced hypoglycemia on plasma oxytocin levels in bulimia and anorexia nervosa. Metabolism 40, 1226–1230 (1991).

    Article  CAS  PubMed  Google Scholar 

  66. Lawson, E. A. et al. Decreased nocturnal oxytocin levels in anorexia nervosa are associated with low bone mineral density and fat mass. J. Clin. Psychiatry 72, 1546–1551 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Afinogenova, Y. et al. Low fasting oxytocin levels are associated with psychopathology in anorexia nervosa in partial recovery. J. Clin. Psychiatry 77, e1483–e1490 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  68. Monteleone, A. M., Scognamiglio, P., Volpe, U., Di Maso, V. & Monteleone, P. Investigation of oxytocin secretion in anorexia nervosa and bulimia nervosa: relationships to temperament personality dimensions. Eur. Eat. Disord. Rev. 24, 52–56 (2016).

    Article  PubMed  Google Scholar 

  69. Lawson, E. A. et al. Oxytocin secretion is associated with severity of disordered eating psychopathology and insular cortex hypoactivation in anorexia nervosa. J. Clin. Endocrinol. Metab. 97, E1898–E1908 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Kim, Y. R., Kim, J. H., Kim, C. H., Shin, J. G. & Treasure, J. Association between the oxytocin receptor gene polymorphism (rs53576) and bulimia nervosa. Eur. Eat. Disord. Rev. 23, 171–178 (2015).

    Article  PubMed  Google Scholar 

  71. Acevedo, S. F., Valencia, C., Lutter, M. & McAdams, C. J. Severity of eating disorder symptoms related to oxytocin receptor polymorphisms in anorexia nervosa. Psychiatry Res. 228, 641–648 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Connelly, J. J. et al. Personality, behavior and environmental features associated with OXTR genetic variants in British mothers. PLoS ONE 9, e90465 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Micali, N., Crous-Bou, M., Treasure, J. & Lawson, E. A. Association between oxytocin receptor genotype, maternal care, and eating disorder behaviours in a community sample of women. Eur. Eat. Disord. Rev. 25, 19–25 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  74. Kim, Y.R., Eom, J.S., Yang, J.W., Kang, J. & Treasure, J. The impact of oxytocin on food intake and emotion recognition in patients with eating disorders: a double blind single dose within-subject cross-over design. PLoS ONE 10, e0137514 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Kuppens, R. J., Donze, S. H. & Hokken-Koelega, A. C. Promising effects of oxytocin on social and food-related behaviour in young children with Prader-Willi syndrome: a randomized, double-blind, controlled crossover trial. Clin. Endocrinol. 85, 979–987 (2016).

    Article  CAS  Google Scholar 

  76. Thienel, M. et al. Oxytocin's inhibitory effect on food intake is stronger in obese than normal-weight men. Int. J. Obes. 40, 1707–1714 (2016).

    Article  CAS  Google Scholar 

  77. Ohlsson, B., Bjorgell, O., Ekberg, O. & Darwiche, G. The oxytocin/vasopressin receptor antagonist atosiban delays the gastric emptying of a semisolid meal compared to saline in human. BMC Gastroenterol. 6, 11 (2006).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Borg, J. & Ohlsson, B. Oxytocin prolongs the gastric emptying time in patients with diabetes mellitus and gastroparesis, but does not affect satiety or volume intake in patients with functional dyspepsia. BMC Res. Notes 5, 148 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Borg, J., Simren, M. & Ohlsson, B. Oxytocin reduces satiety scores without affecting the volume of nutrient intake or gastric emptying rate in healthy subjects. Neurogastroenterol. Motil. 23, 56–61 (2011).

    Article  CAS  PubMed  Google Scholar 

  80. Striepens, N. et al. Oxytocin enhances cognitive control of food craving in women. Hum. Brain Mapp. 37, 4276–4285 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  81. Herisson, F. M. et al. Oxytocin acting in the nucleus accumbens core decreases food intake. J. Neuroendocrinol. http://dx.doi.org/10.1111/jne.12381 (2016).

  82. Petring, O. U. The effect of oxytocin on basal and pethidine-induced delayed gastric emptying. Br. J. Clin. Pharmacol. 28, 329–332 (1989).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Ohlsson, B., Ringstrom, G., Abrahamsson, H., Simren, M. & Bjornsson, E. S. Oxytocin stimulates colonic motor activity in healthy women. Neurogastroenterol. Motil. 16, 233–240 (2004).

    Article  CAS  PubMed  Google Scholar 

  84. Louvel, D. et al. Oxytocin increases thresholds of colonic visceral perception in patients with irritable bowel syndrome. Gut 39, 741–747 (1996).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Vila, G. et al. Systemic administration of oxytocin reduces basal and lipopolysaccharide-induced ghrelin levels in healthy men. J. Endocrinol. 203, 175–179 (2009).

    Article  CAS  PubMed  Google Scholar 

  86. Blevins, J. E. 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. 310, R640–R658 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  87. Pischon, T. et al. General and abdominal adiposity and risk of death in Europe. N. Engl. J. Med. 359, 2105–2120 (2008).

    Article  CAS  PubMed  Google Scholar 

  88. 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. 13, 213–222 (1989).

    CAS  PubMed  Google Scholar 

  89. Schorr, M. et al. Oxytocin and its relationship to body composition, bone mineral density, and hip geometry across the weight spectrum. J. Clin. Endocrinol. Metab. 102, 2814–2824 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  90. Lawson, E. A. et al. Oxytocin secretion is related to measures of energy homeostasis in young amenorrheic athletes. J. Clin. Endocrinol. Metab. 99, E881–E885 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Szulc, P. et al. High serum oxytocin is associated with metabolic syndrome in older men - The MINOS study. Diabetes Res. Clin. Pract. 122, 17–27 (2016).

    Article  CAS  PubMed  Google Scholar 

  92. Qian, W. et al. Decreased circulating levels of oxytocin in obesity and newly diagnosed type 2 diabetic patients. J. Clin. Endocrinol. Metab. 99, 4683–4689 (2014).

    Article  CAS  PubMed  Google Scholar 

  93. Burt, R. L., Leake, N. H. & Dannenburg, W. N. Effect of synthetic oxytocin on plasma nonesterified fatty acids, triglycerides, and blood glucose. Obstet. Gynecol. 21, 708–712 (1963).

    CAS  PubMed  Google Scholar 

  94. Leibel, R. L., Rosenbaum, M. & Hirsch, J. Changes in energy expenditure resulting from altered body weight. N. Engl. J. Med. 332, 621–628 (1995).

    Article  CAS  PubMed  Google Scholar 

  95. Plante, E. et al. Oxytocin treatment prevents the cardiomyopathy observed in obese diabetic male db/db mice. Endocrinology 156, 1416–1428 (2015).

    Article  CAS  PubMed  Google Scholar 

  96. Altirriba, J., Poher, A. L. & Rohner-Jeanrenaud, F. Chronic oxytocin administration as a treatment against impaired leptin signaling or leptin resistance in obesity. Front. Endocrinol. (Lausanne) 6, 119 (2015).

    Article  Google Scholar 

  97. Olszewski, P. K., Klockars, A. & Levine, A. S. Oxytocin and potential benefits for obesity treatment. Curr. Opin. Endocrinol. Diabetes Obes. http://dx.doi.org/10.1097/MED.0000000000000351 (2017).

  98. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02849743?term=02849743&rank=1 (2017).

  99. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT03043053?term=03043053&rank=1 (2017).

  100. US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT03119610?term=03119610&rank=1 (2017).

  101. Wheeler, E. et al. Genome-wide SNP and CNV analysis identifies common and low-frequency variants associated with severe early-onset obesity. Nat. Genet. 45, 513–517 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  102. Martin, A. et al. Cerebrospinal fluid levels of oxytocin in Prader-Willi syndrome: a preliminary report. Biol. Psychiatry 44, 1349–1352 (1998).

    Article  CAS  PubMed  Google Scholar 

  103. 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. 80, 573–579 (1995).

    CAS  PubMed  Google Scholar 

  104. Bush, N. R. et al. Socioeconomic disparities in childhood obesity risk: association with an oxytocin receptor polymorphism. JAMA Pediatr. 171, 61–67 (2017).

    Article  PubMed  Google Scholar 

  105. Yanovski, S. Z. & Yanovski, J. A. Long-term drug treatment for obesity: a systematic and clinical review. JAMA 311, 74–86 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  106. Bray, G. A. Obesity in adults: drug therapy. UpToDate https://www.uptodate.com/contents/obesity-in-adults-drug-therapy?source=search_result&search=weight%20loss%20medication&selectedTitle=1150 (2017).

  107. Einfeld, S. L. et al. A double-blind randomized controlled trial of oxytocin nasal spray in Prader Willi syndrome. Am. J. Med. Genet. A 164, 2232–2239 (2014).

    Article  CAS  Google Scholar 

  108. Bobbioni-Harsch, E. et al. Physiological concentrations of oxytocin powerfully stimulate insulin secretion in vitro. Endocrine 3, 55–59 (1995).

    Article  CAS  PubMed  Google Scholar 

  109. Bjorkstrand, E., Eriksson, M. & Uvnas-Moberg, K. Evidence of a peripheral and a central effect of oxytocin on pancreatic hormone release in rats. Neuroendocrinology 63, 377–383 (1996).

    Article  CAS  PubMed  Google Scholar 

  110. Maejima, Y. et al. Nasal oxytocin administration reduces food intake without affecting locomotor activity and glycemia with c-Fos induction in limited brain areas. Neuroendocrinology 101, 35–44 (2015).

    Article  CAS  PubMed  Google Scholar 

  111. Elabd, S. & Sabry, I. Two birds with one stone: possible dual-role of oxytocin in the treatment of diabetes and osteoporosis. Front. Endocrinol. (Lausanne) 6, 121 (2015).

    Article  Google Scholar 

  112. Spellacy, W. N., Carlson, K. L. & Birk, S. A. Effect of posterior pituitary hormones on blood glucose and plasma insulin levels in postpartum patients. Obstet. Gynecol. 28, 355–359 (1966).

    CAS  PubMed  Google Scholar 

  113. Chiodera, P. et al. Effect of pharmacological doses of oxytocin on insulin response to glucose in normal man. Horm. Res. 20, 150–154 (1984).

    Article  CAS  PubMed  Google Scholar 

  114. Paolisso, G. et al. Pharmacological doses of oxytocin affect plasma hormone levels modulating glucose homeostasis in normal man. Horm. Res. 30, 10–16 (1988).

    Article  CAS  PubMed  Google Scholar 

  115. Paolisso, G. et al. Effects of oxytocin delivery on counter-regulatory hormone response in insulin-dependent (type 1) diabetic subjects. Horm. Res. 31, 250–255 (1989).

    Article  CAS  PubMed  Google Scholar 

  116. Paolisso, G. et al. Effects of oxytocin upon the endocrine pancreas secretion and glucose turnover in normal man. Acta Endocrinol. (Copenh.) 123, 504–510 (1990).

    Article  CAS  Google Scholar 

  117. Klement, J. et al. Oxytocin improves beta-cell responsivity and glucose tolerance in healthy men. Diabetes 66, 264–271 (2016).

    Article  CAS  PubMed  Google Scholar 

  118. Kujath, A. S. et al. Oxytocin levels are lower in premenopausal women with type 1 diabetes mellitus compared with matched controls. Diabetes Metab. Res. Rev. 31, 102–112 (2015).

    Article  CAS  PubMed  Google Scholar 

  119. Nieman, L. K. Cushing's Syndrome: update on signs, symptoms and biochemical screening. Eur. J. Endocrinol. 173, M33–M38 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  120. Bathgate, R. A. & Sernia, C. Characterization of vasopressin and oxytocin receptors in an Australian marsupial. J. Endocrinol. 144, 19–29 (1995).

    Article  CAS  PubMed  Google Scholar 

  121. Legros, J. J., Chiodera, P., Geenen, V., Smitz, S. & von Frenckell, R. Dose-response relationship between plasma oxytocin and cortisol and adrenocorticotropin concentrations during oxytocin infusion in normal men. J. Clin. Endocrinol. Metab. 58, 105–109 (1984).

    Article  CAS  PubMed  Google Scholar 

  122. Legros, J. J., Chiodera, P. & Demey-Ponsart, E. Inhibitory influence of exogenous oxytocin on adrenocorticotropin secretion in normal human subjects. J. Clin. Endocrinol. Metab. 55, 1035–1039 (1982).

    Article  CAS  PubMed  Google Scholar 

  123. Heinrichs, M., Baumgartner, T., Kirschbaum, C. & Ehlert, U. Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress. Biol. Psychiatry 54, 1389–1398 (2003).

    Article  CAS  PubMed  Google Scholar 

  124. Linnen, A. M., Ellenbogen, M. A., Cardoso, C. & Joober, R. Intranasal oxytocin and salivary cortisol concentrations during social rejection in university students. Stress 15, 393–402 (2012).

    Article  CAS  PubMed  Google Scholar 

  125. Cardoso, C., Kingdon, D. & Ellenbogen, M. A. A meta-analytic review of the impact of intranasal oxytocin administration on cortisol concentrations during laboratory tasks: moderation by method and mental health. Psychoneuroendocrinology 49, 161–170 (2014).

    Article  CAS  PubMed  Google Scholar 

  126. Page, S. R. et al. The effect of oxytocin infusion on adenohypophyseal function in man. Clin. Endocrinol. 32, 307–313 (1990).

    Article  CAS  Google Scholar 

  127. Vallera, C., Choi, L. O., Cha, C. M. & Hong, R. W. Uterotonic medications: oxytocin, methylergonovine, carboprost. misoprostol. Anesthesiol. Clin. 35, 207–219 (2017).

    Article  PubMed  Google Scholar 

  128. Vankrieken, L., Godart, A. & Thomas, K. Oxytocin determination by radioimmunoassay. Gynecol. Obstet. Invest. 16, 180–185 (1983).

    Article  CAS  PubMed  Google Scholar 

  129. Fabian, M., Forsling, M. L., Jones, J. J. & Pryor, J. S. The clearance and antidiuretic potency of neurohypophysial hormones in man, and their plasma binding and stability. J. Physiol. 204, 653–668 (1969).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  130. 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. 262, 143–149 (1983).

    Article  CAS  PubMed  Google Scholar 

  131. Jones, P. M. & Robinson, I. C. Differential clearance of neurophysin and neurohypophysial peptides from the cerebrospinal fluid in conscious guinea pigs. Neuroendocrinology 34, 297–302 (1982).

    Article  CAS  PubMed  Google Scholar 

  132. MacDonald, E. et al. A review of safety, side-effects and subjective reactions to intranasal oxytocin in human research. Psychoneuroendocrinology 36, 1114–1126 (2011).

    Article  CAS  PubMed  Google Scholar 

  133. Nissen, E. et al. Different patterns of oxytocin, prolactin but not cortisol release during breastfeeding in women delivered by caesarean section or by the vaginal route. Early Hum. Dev. 45, 103–118 (1996).

    Article  CAS  PubMed  Google Scholar 

  134. Ueda, T., Yokoyama, Y., Irahara, M. & Aono, T. Influence of psychological stress on suckling-induced pulsatile oxytocin release. Obstet. Gynecol. 84, 259–262 (1994).

    CAS  PubMed  Google Scholar 

  135. Fuchs, A. R. et al. Oxytocin secretion and human parturition: pulse frequency and duration increase during spontaneous labor in women. Am. J. Obstet. Gynecol. 165, 1515–1523 (1991).

    Article  CAS  PubMed  Google Scholar 

  136. Baskaran, C. et al. Oxytocin secretion is pulsatile in men and is related to social-emotional functioning. Psychoneuroendocrinology 85, 28–23 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  137. Hoover, R. T. Intranasal oxytocin in eighteen hundred patients. A study on its safety as used in a community hospital. Am. J. Obstet. Gynecol. 110, 788–794 (1971).

    Article  CAS  PubMed  Google Scholar 

  138. Borglin, N. E. Intranasal administration of oxytocin for induction and stimulation of labour. Acta Obstet. Gynecol. Scand. 41, 238–253 (1962).

    Article  CAS  PubMed  Google Scholar 

  139. Okamoto, Y., Ishitobi, M., Wada, Y. & Kosaka, H. The potential of nasal oxytocin administration for remediation of autism spectrum disorders. CNS Neurol. Disord. Drug Targets 15, 564–577 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  140. Anagnostou, E. et al. Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders: a randomized controlled trial. Mol. Autism 3, 16 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  141. Anagnostou, E. et al. Intranasal oxytocin in the treatment of autism spectrum disorders: a review of literature and early safety and efficacy data in youth. Brain Res. 1580, 188–198 (2014).

    Article  CAS  PubMed  Google Scholar 

  142. Tachibana, M. et al. Long-term administration of intranasal oxytocin is a safe and promising therapy for early adolescent boys with autism spectrum disorders. J. Child Adolesc. Psychopharmacol. 23, 123–127 (2013).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The author acknowledges support from the NIH under award number R01DK109932.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Elizabeth A. Lawson.

Ethics declarations

Competing interests

E.A.L. is on the Scientific Advisory Board of OXT Therapeutics, Inc. E.A.L. has a financial interest in OXT Therapeutics, Inc., a company developing an intranasal oxytocin and long-acting analogues of oxytocin to treat obesity and metabolic disease. E.A.L.'s interests were reviewed and are managed by Massachusetts General Hospital and Partners HealthCare in accordance with their conflicts-of-interest policy.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lawson, E. The effects of oxytocin on eating behaviour and metabolism in humans. Nat Rev Endocrinol 13, 700–709 (2017). https://doi.org/10.1038/nrendo.2017.115

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrendo.2017.115

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing