ESPE Abstracts (2016) 86 P-P1-738

Oxytocin Deficiency is Associated with Hyperphagia and Weight Gain in Hypothalamic and Common Obesity: A First-in-Humans Proof-of-Concept Study

Hoong-Wei Gana,b, Clare Leesonb, Helen Aitkenheadb, Helen Spoudeasb, Juan Pedro Martinez-Barberaa & Mehul Dattania,b

aUniversity College London Institute of Child Health, London, UK; bGreat Ormond Street Hospital for Children NHS Foundation Trust, London, UK

Background: Hypothalamic obesity (HyOb) is a rare form of treatment-resistant morbid obesity associated with congenital or acquired hypothalamic damage. Its pathophysiology has been attributed to hyperphagia and hyperinsulinaemia. The wider roles of oxytocin (OXT) in regulating appetite and weight have recently emerged in animal and human studies, but there is no human evidence that hypo-oxytocinaemia contributes to weight gain.

Hypothesis: Hypo-oxytocinaemia is associated with an increase in appetite and weight in HyOb.

Method: Fasting and oral glucose-stimulated OXT concentrations in HyOb and lean (HyLean) children with hypothalamic damage were determined by internally validated ELISA comparing them to age-matched common obesity (Ob) and lean controls. Hyperphagia was quantified using the Dykens’ Hyperphagia Questionnaire Score (DHQS).

Results: Patients (42 HyOb, 15 HyLean, 22 Ob, 14 Lean; 52.7% male) were of median age 11.8 (8.6–14.4) years with a BMI SDS of +2.8 (+2.5 – +3.1) and +1.0 (−0.1 – +1.7) in the obese and lean groups respectively. HyOb patients had a higher DHQS compared to lean controls (25 (15–34) vs 16 (11–21), P=0.009), but not HyLean (22 (14–30), P=NS) or Ob (23 (17–28), P=NS) patients. Although not statistically significant, fasting OXT concentrations were lower in both HyOb (98.5 (78.9–123.1) pg/ml) and Ob (101.8 (82.3–125.8) pg/ml) patients compared to HyLean (145.2 (80.1–169.3) pg/ml) and lean (133.1 (71.6–157.9) pg/ml) controls (P=NS for all comparisons). OXT concentrations were negatively correlated with DHQS (ρ=−0.3, P=0.02) and not stimulated by an oral glucose load.

Conclusion: This study supports the role of OXT as an anorexigen, suggesting that hypo-oxytocinaemia is common to all human obesity. Hyperphagia is not unique to HyOb, is associated with hypo-oxytocinaemia and is present in all forms of obesity. Further recruitment to power this study (n=120) and paediatric trials of OXT supplementation will help confirm this theory and determine its efficacy in treating childhood obesity.

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