Hyperphagia, leptin, and brain-derived neurotrophic factor in subjects with Alström syndrome and BMI-Z matched controls

Thursday, October 11, 2012 — Poster Session III
10:00 a.m. – Noon	Natcher Conference Center, Building 45	NICHD	EPIGEN/TRANS/CHROM-1

Authors

• MD Hicks
• JD Marshall
• P Maffei
• AE Hanish
• LA Hunter
• SM Brady
• NM Sedaka
• R Sherafat Kazemzadeh
• JW Tsao
• G Milan
• J Naggert
• JA Yanovski
• JC Han

Abstract

Background: Alström syndrome (AS) is associated with early-onset obesity and is caused by mutations in ALMS1 which has been identified in mouse models to play an important role in the primary cilia of hypothalamic neurons. Leptin and its downstream mediator, brain-derived neurotrophic factor (BDNF), act within the hypothalamus to decrease appetite. Studies assessing hyperphagia and the leptin pathway have not been previously reported in patients with AS. Methods: 35 subjects with AS were matched with 70 controls by age, sex, and body mass index Z-score (BMI-Z). Fasting serum leptin and BDNF were measured by commercial ELISA. Parents of children ages 4-17 years also completed a hyperphagia questionnaire. Results: Subjects with AS had 34% higher hyperphagia score (p=0.04) and 68% higher leptin (p<0.001) than control subjects. BDNF was similar between groups (p=0.66), but BDNF/leptin ratio was 62% lower in AS compared with controls (p=0.03). Conclusions: Subjects with AS have greater hyperphagia scores, higher leptin concentrations, and lower BDNF/leptin ratios than controls subjects of similar body size. These findings support a potential role for ALMS1 in energy homeostasis within the hypothalamus and suggest that a dysfunction in leptin-mediated appetite regulation may underlie the pathophysiology of obesity in AS.

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