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

Abstract

The fact that more than 78 million adults in the US are considered overweight or obese highlights the need to develop new, effective strategies to treat obesity and its associated complications, including type 2 diabetes, kidney disease and cardiovascular disease. While the neurohypophyseal peptide oxytocin (OT) is well recognized for its peripheral effects to stimulate uterine contraction during parturition and milk ejection during lactation, release of OT within the brain is implicated in prosocial behaviors and in the regulation of energy balance. Previous findings indicate that chronic administration of OT decreases food intake and weight gain or elicits weight loss in diet-induced obese (DIO) mice and rats. Furthermore, chronic systemic treatment with OT largely reproduces the effects of central administration to reduce weight gain in DIO and genetically obese rodents at doses that do not appear to result in tolerance. These findings have now been recently extended to more translational models of obesity showing that chronic subcutaneous or intranasal OT treatment is sufficient to elicit body weight loss in DIO nonhuman primates and pre-diabetic obese humans. This review assesses the potential use of OT as a therapeutic strategy for treatment of obesity in rodents, nonhuman primates, and humans, and identifies potential mechanisms that mediate this effect.

Keywords: Energy expenditure; Food intake; Obesity; Oxytocin.

Fig. 1.

A schematic of circuitry that potentially contributes to the effectiveness of OT on energy homeostasis. OT release within the CNS, spinal cord, and from the neurohypophysis into the circulation (shown in black arrows) may impact metabolic processes (shown in gray) that result in the reduction of bodyweight. Dotted arrow represents implicated pathways from sympathetic preganglionic neurons in the spinal cord to WAT [149,150]. Reported opposing effects denoted by arrows pointed in opposite directions to one another. Abbreviation: ARC, arcuate nucleus; CCK, cholecystokinin; BAT, brown adipose tissue; NTS, nucleus of the solitary tract; PVN, paraventricular nucleus; SON, supraoptic nucleus; and VTA, ventral tegmental area. This figure has been modified from a previous manuscript [Endocrinology Coming full circle: contributions of central and peripheral oxytocin actions to energy balance 154(2):589–96, 2013; http://www.ncbi.nlm.nih.gov/pubmed/23270805].