There is growing evidence that oxytocin (OXT), a hypothalamic hormone well recognized for its effects in inducing parturition and lactation, has important metabolic effects in both sexes. The purpose of this review is to summarize the physiologic effects of OXT on metabolism and to explore its therapeutic potential for metabolic disorders. In model systems, OXT promotes weight loss by decreasing energy intake. Pair-feeding studies suggest that OXT-induced weight loss may also be partly due to increased energy expenditure and/or lipolysis. In humans, OXT appears to modulate both homeostatic and reward-driven food intake, although the observed response depends on nutrient milieu (eg, obese vs. nonobese), clinical characteristics (eg, sex), and experimental paradigm. In animal models, OXT is anabolic to muscle and bone, which is consistent with OXT-induced weight loss occurring primarily via fat loss. In some human observational studies, circulating OXT concentrations are also positively associated with lean mass and bone mineral density. The impact of exogenous OXT on human obesity is the focus of ongoing investigation. Future randomized, placebo-controlled clinical trials in humans should include rigorous, standardized, and detailed assessments of adherence, adverse effects, pharmacokinetics/pharmacodynamics, and efficacy in the diverse populations that may benefit from OXT, in particular those in whom hypothalamic OXT signaling may be abnormal or impaired (eg, individuals with Sim1 deficiency, Prader-Willi syndrome, or craniopharyngioma). Future studies will also have the opportunity to investigate the characteristics of new OXT mimetic peptides and the obligation to consider long-term effects, especially when OXT is given to children and adolescents. (Endocrine Reviews XX: XX - XX, 2020).
Keywords: body composition; energy balance; feeding behavior; metabolism; oxytocin.
Published by Oxford University Press on behalf of the Endocrine Society 2019.