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Elevated Peptide YY Levels in Adolescent Girls with Anorexia Nervosa

Neuroendocrine Unit (M.M., K.K.M., P.T., K.G., A.L., N.L., A.K.), Pediatric Endocrine Unit (M.M.), and Eating Disorders Unit (D.B.H.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114

Address all correspondence and requests for reprints to: Anne Klibanski, M.D., BUL 457, Neuroendocrine Unit, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114. 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 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 body mass index (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). Body mass index, fat mass, REE, GH, and T₃ explained 68% of the variability of log PYY. Log PYY predicted percentage of 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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