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Submitted on August 22, 2005
Accepted on November 1, 2005
Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Pediatric Endocrine Unit, MassGeneral Hospital for Children and Harvard Medical School, Eating Disorders Unit, Massachusetts General Hospital and Harvard Medical School
* To whom correspondence should be addressed. E-mail: aklibanski{at}partners.org.
Background: Peptide YY (PYY) is an intestinally derived anorexigen that acts via the Y2 receptor, and Y2 receptor deletion in rodents increases bone formation. Anorexia nervosa (AN) is associated with a deliberate reduction in food intake and low bone density, but endocrine modulators of food intake in AN are not known. In addition, known regulators of bone turnover such as growth hormone (GH), cortisol and estrogen explain only a fraction of the variability in bone turnover marker levels. Hypotheses: We hypothesized that PYY may be elevated in AN compared with controls and may contribute to decreased food intake and bone formation. Methods: Fasting PYY was examined in 23 AN girls and 21 healthy adolescents 12-18 yr old. We also examined GH, cortisol, ghrelin and leptin (overnight frequent sampling), and fasting IGF-I, estradiol, total T3 and bone markers. Macronutrient intake and resting energy expenditure (REE) were measured. Results: AN girls had higher PYY levels compared with controls (17.8 ± 10.2 vs. 4.8 ± 4.3 pg/ml, P < 0.0001). Predictors of log PYY were nutritional markers including BMI (r = -0.62, P < 0.0001), fat mass (r = -0.55, P = 0.0003) and REE (r -0.51, P = 0.0006), and hormones including GH (r = 0.38, P = 0.004) and T3 (r = -0.59, P = 0.0001). BMI, fat mass, REE, GH and T3 explained 68% of the variability of log PYY. Log PYY predicted %calories from fat (r = -0.56, P = 0.0002), and independently predicted osteocalcin (r = -0.45, P = 0.003), bone specific alkaline phosphatase (r = -0.46, P = 0.003), N-telopeptide/creatinine (r = -0.55, P = 0.0003) and deoxypyridinoline/creatinine (r = -0.52, P = 0.001) on regression modeling. Conclusion: Elevated PYY may contribute to reduced intake and decreased bone turnover in AN.
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