Chronic Oxytocin Administration as a Treatment Against Impaired Leptin Signaling or Leptin Resistance in Obesity

Abstract

This review summarizes the existing literature on the effects of oxytocin administration in the treatment of obesity in different animal models and in humans, focusing on the central control of food intake, the oxytocin effects on adipose tissue, and the relationships between oxytocin and leptin. Oxytocin is a hypothalamic nonapeptide synthesized mainly in the paraventricular and supraoptic nuclei projecting to the pituitary, where it reaches the peripheral circulation, as well as to other brain regions. Moreover, leptin modulates oxytocin levels and activates oxytocin neurons in the hypothalamic paraventricular nucleus, which innervates the nucleus of the solitary tract, partly responsible for the brain-elicited oxytocin effects. Taking into account that oxytocin is located downstream leptin, it was hypothesized that oxytocin treatment would be effective in decreasing body weight in leptin-resistant DIO animals, as well as in those with leptin or with leptin receptor deficiency. Several groups have demonstrated that in such animal models (rats, mice, and rhesus monkeys), central or peripheral oxytocin administration decreases body weight, mainly due to a decrease in fat mass, demonstrating that an oxytocin treatment is able to partly overcome leptin deficiency or resistance. Moreover, a pilot clinical study demonstrated the efficiency of oxytocin in the treatment of obesity in human subjects, confirming the results obtained in the different animal models. Larger multicenter studies are now needed to determine whether the beneficial effects of oxytocin treatment can apply not only to obese but also to type 2 diabetic patients. These studies should also shed some light on the molecular mechanisms of oxytocin action in humans.

Serum Irisin and Oxytocin Levels as Predictors of Metabolic Parameters in Obese Children

“…Few studies have been performed to determine the circulating levels of oxytocin in obese adults (14,15,16,17,42). Conflicting findings exist regarding whether oxytocin levels are increased (42), unchanged (43), or decreased (16,17) in obese adults.…”

The effects of oxytocin on eating behaviour and metabolism in humans

“…Oxytocin is emerging as a promising novel weight-loss therapy for obesity, as evidenced by review articles published on this topic over the past several years 8,96,97 and current clinical research studies registered on ClinicalTrials.gov (NCT 02849743, 03043053, 03119610). Experiments in rodents and nonhuman primates demonstrate that chronic peripheral or central administration of oxytocin results in sustained weight loss attributed to reduced food intake, maintenance of energy expenditure despite weight loss and increased lipolysis 14,18,37,38,86 .…”

Oxytocin – The Sweet Hormone?

“…In rats, central (intracerebroventricular) injections of oxytocin affect social and sexual behavior, but also potently inhibit appetite [15][16][17], as do central injections of mesotocin in chicks [18]. In mammals, oxytocin is expressed in magnocellular neuroendocrine neurons that project to the neurohypophysis and in parvocellular neurons of the paraventricular nucleus (PVN), subsets of which project to forebrain regions, the caudal brainstem and spinal cord.…”