Oxytocin in metabolic homeostasis: implications for obesity and diabetes management

Abstract

Oxytocin was once understood solely as a neuropeptide with a central role in social bonding, reproduction, parturition, lactation and appetite regulation. Recent evidence indicates that oxytocin enhances glucose uptake and lipid utilization in adipose tissue and skeletal muscle, suggesting that dysfunction of the oxytocin system could underlie the pathogenesis of insulin resistance and dyslipidaemia. Murine studies revealed that deficiencies in oxytocin signalling and oxytocin receptor expression lead to obesity despite normal food intake, motor activity and increased leptin levels. In addition, plasma oxytocin concentration is notably lower in obese individuals with diabetes, which may suggest an involvement of the oxytocin system in the pathogenesis of cardiometabolic disease. More recently, small scale studies demonstrated that intranasal administration of oxytocin was associated with significant weight loss as well as improvements in insulin sensitivity and pancreatic β-cell responsivity in human subjects. The multi-pronged effects of oxytocin signalling on improving peripheral insulin sensitivity, pancreatic function and lipid homeostasis strongly suggest a role for this system as a therapeutic target in obesity and diabetes management. The complexity of obesity aetiology and the pathogenesis of obesity-related metabolic complications underscore the need for a systems approach to better understand the role of oxytocin in metabolic function.

Keywords: beta cell function; glucose metabolism; insulin sensitivity; lipid metabolism.

Figure 1

Identified tissue targets in the murine and human oxytocin system for treatment of metabolic dysfunction associated with the development of obesity and diabetes. Abbreviations: DIO, diet‐induced obesity; FABP4, fatty acid binding protein 4; NEFA, non‐esterified fatty acids; ob/ob, obese leptin‐deficient mouse model. [Colour figure can be viewed at wileyonlinelibrary.com]