Objective Preclinical studies indicate that oxytocin is anorexigenic and has beneficial metabolic effects. Oxytocin effects on nutrition and metabolism in humans are not well defined. We hypothesized that oxytocin would reduce caloric intake and appetite, and alter levels of appetite-regulating hormones. We also explored metabolic effects of oxytocin. Methods We performed a randomized, placebo-controlled crossover study of single-dose intranasal oxytocin (24 IU) in 25 fasting healthy men. After oxytocin/placebo, subjects selected breakfast from a menu, and were given double portions. Caloric content of food consumed was measured. Visual analogue scales were used to assess appetite and blood was drawn for appetite-regulating hormones, insulin, and glucose before and after oxytocin/placebo. Indirect calorimetry assessed resting energy expenditure (REE) and substrate utilization. Results Oxytocin reduced caloric intake with a preferential effect on fat intake and increased levels of the anorexigenic hormone cholecystokinin without affecting appetite or other appetite-regulating hormones. There was no effect of oxytocin on REE. Oxytocin resulted in a shift from carbohydrate to fat utilization and improved insulin sensitivity. Conclusions Intranasal oxytocin reduces caloric intake and has beneficial metabolic effects in men without concerning side effects. The efficacy and safety of sustained oxytocin administration in the treatment of obesity warrants investigation.

Objective Anorexia nervosa, a psychiatric disorder characterized by self-induced starvation, is associated with endocrine dysfunction and comorbid anxiety and depression. Animal data suggest that oxytocin may have anxiolytic and antidepressant effects. We have reported increased postprandial oxytocin levels in women with active anorexia nervosa (AN), and decreased levels in weight-recovered women with anorexia nervosa (ANWR) compared to healthy controls (HC). A meal may represent a significant source of stress in patients with disordered eating. We therefore investigated the association between post-prandial oxytocin secretion and symptoms of anxiety and depression in anorexia nervosa. Method We performed a cross-sectional study of 35 women (13 AN, 9 ANWR and 13 HC). Serum oxytocin and cortisol and plasma leptin levels were measured fasting and 30, 60, and 120min after a standardized mixed meal. The area under the curve (AUC), and for oxytocin, postprandial nadir and peak levels were determined. Anxiety and depressive symptoms were assessed using the Spielberger State-Trait Anxiety Inventory (STAI) and Beck Depression Inventory II (BDI-II). Results In women with anorexia nervosa, oxytocin AUC and post-prandial nadir and peak levels were positively associated with STAI scores. Oxytocin AUC and nadir levels were positively associated with BDI-II scores. After controlling for cortisol AUC, most relationships remained significant. After controlling for leptin AUC, all of the relationships remained significant. Oxytocin secretion explained up to 51% of the variance in STAI trait and 24% of BDI-II scores. Conclusions Abnormal post-prandial oxytocin secretion in women with anorexia nervosa is associated with increased symptoms of anxiety and depression. This may represent an adaptive response of oxytocin secretion to food-related symptoms of anxiety and depression.

Objective Corticotropin releasing hormone (CRH)-mediated hypercortisolemia has been demonstrated in anorexia nervosa (anorexia), a psychiatric disorder characterized by food restriction despite low body weight. While CRH is anorexigenic, downstream cortisol stimulates hunger. Using a food-related fMRI paradigm, we have demonstrated hypoactivation of brain regions involved in food motivation in women with anorexia, even after weight-recovery. The relationship between hypothalamic-pituitary-adrenal (HPA) axis dysregulation and appetite, and the association with food motivation neurocircuitry hypoactivation is unknown in anorexia. We investigated the relationship between HPA activity, appetite and food motivation neurocircuitry hypoactivation in anorexia. Design Cross-sectional study of 36 women [13 anorexia (AN), 10 weight-recovered AN (ANWR), 13 healthy controls (HC)]. Methods Peripheral cortisol and ACTH levels were measured fasting and 30, 60, and 120min after a standardized mixed meal. The Visual Analogue Scale was used to assess homeostatic and hedonic appetite. fMRI was performed during visual processing of food and non-food stimuli to measure brain activation pre- and post-meal. Results In each group, serum cortisol levels decreased following the meal. Mean fasting, 120min post-meal, and nadir cortisol levels were high in AN vs. HC. Mean postprandial ACTH levels were high in ANWR compared to HC and AN. Cortisol levels were associated with lower fasting homeostatic and hedonic appetite, independent of BMI and depressive symptoms. Cortisol levels were also associated with between-group variance in activation in food-motivation brain regions (e.g., hypothalamus, amygdala, hippocampus, OFC and insula). Conclusions HPA activation may contribute to the maintenance of anorexia by suppression of appetitive drive.

ClinicalTrials.gov identifier: NCT01642550.